VCV000002164.78 - ClinVar

NM_213599.3(ANO5):c.191dup (p.Asn64fs)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(38)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic/Likely pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

This variant is part of a Genotype

NM_213599.2(ANO5):c.[155A>G];[191dupA]

Identifiers

NM_213599.3(ANO5):c.191dup (p.Asn64fs)

Variation ID: 2164 Accession: VCV000002164.78

Type and length

Duplication, 1 bp

Location

Cytogenetic: 11p14.3 11: 22221100-22221101 (GRCh38) [ NCBI UCSC ] 11: 22242646-22242647 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jul 23, 2014	Oct 26, 2024	Aug 16, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_213599.3:c.191dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_998764.1:p.Asn64fs	frameshift
NM_213599.3:c.191dupA MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_001142649.1:c.188dupA
NM_001142649.2:c.188dup	NP_001136121.1:p.Asn63fs	frameshift
NM_213599.2:c.191dupA
NC_000011.10:g.22221107dup
NC_000011.9:g.22242653dup
NG_015844.1:g.32932dup
LRG_868:g.32932dup

... more HGVS ... less HGVS

Protein change

N63fs, N64fs

Other names

Canonical SPDI

NC_000011.10:22221100:AAAAAAA:AAAAAAAA

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

OMIM: 608662.0004 dbSNP: rs137854521 ClinGen: CA115378 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
ANO5		-	-	GRCh38 GRCh37	1290	1326

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Autosomal recessive limb-girdle muscular dystrophy type 2L	Pathogenic/Likely pathogenic (10)	criteria provided, multiple submitters, no conflicts	Aug 16, 2024	RCV000002248.33
Miyoshi muscular dystrophy 3	Pathogenic (1)	no assertion criteria provided	Mar 20, 2012	RCV000002247.11
not provided	Pathogenic (14)	criteria provided, multiple submitters, no conflicts	Feb 1, 2024	RCV000082844.61
Myopathy	Pathogenic (1)	criteria provided, single submitter	Oct 2, 2015	RCV000414931.5
Autosomal recessive limb-girdle muscular dystrophy type 2L Gnathodiaphyseal dysplasia	Pathogenic (1)	criteria provided, single submitter	Jan 30, 2024	RCV000627781.12
Achilles tendon contracture Elevated circulating creatine kinase concentration Lower limb amyotrophy Lower limb muscle weakness Polycystic kidney disease	Pathogenic (1)	criteria provided, single submitter	Jan 1, 2017	RCV000627021.5
ANO5-related disorder	Pathogenic (3)	criteria provided, single submitter	Aug 29, 2018	RCV000778317.11
Gnathodiaphyseal dysplasia	Pathogenic (2)	criteria provided, multiple submitters, no conflicts	May 4, 2022	RCV001196017.9
Intellectual disability	Likely benign (1)	no assertion criteria provided	Jan 1, 2019	RCV001251667.5
Autosomal recessive limb-girdle muscular dystrophy	Pathogenic (2)	criteria provided, multiple submitters, no conflicts	Feb 5, 2024	RCV002307353.5
Autosomal recessive limb-girdle muscular dystrophy type 2L Gnathodiaphyseal dysplasia Miyoshi muscular dystrophy 3	Pathogenic (1)	criteria provided, single submitter	Aug 21, 2021	RCV002476911.4
ANO5-related muscular dystrophy	Pathogenic (1)	criteria provided, single submitter	Aug 2, 2023	RCV003332991.1
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Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Oct 02, 2015)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Myopathy Affected status: yes Allele origin: unknown	Centre for Mendelian Genomics, University Medical Centre Ljubljana Accession: SCV000492753.1 First in ClinVar: Jan 13, 2017 Last updated: Jan 13, 2017
Pathogenic (Jun 26, 2017)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Autosomal recessive limb-girdle muscular dystrophy type 2L (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard Study: Broad Institute Center for Mendelian Genomics (CMG) Accession: SCV000693897.1 First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018	Publications: PubMed (1) PubMed: 21186264 Comment: The c.191dupA pathogenic variant is previously described Founder mutation within the Northern European population (PMID: 21186264). Number of individuals with the variant: 1
Pathogenic (Jan 01, 2017)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Achilles tendon contracture Elevated circulating creatine kinase concentration Lower limb amyotrophy Lower limb muscle weakness Polycystic kidney disease Affected status: yes Allele origin: unknown	Centre for Mendelian Genomics, University Medical Centre Ljubljana Accession: SCV000747724.1 First in ClinVar: May 12, 2018 Last updated: May 12, 2018
Likely pathogenic (Oct 08, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Autosomal recessive limb-girdle muscular dystrophy type 2L Affected status: yes Allele origin: unknown	NeuroMeGen, Hospital Clinico Santiago de Compostela Accession: SCV000882597.1 First in ClinVar: Feb 04, 2019 Last updated: Feb 04, 2019
Pathogenic (Aug 08, 2016)	criteria provided, single submitter (EGL Classification Definitions) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000231252.4 First in ClinVar: Jun 28, 2015 Last updated: Jul 30, 2019 Comment: The c.191dupA ANO5 variant is a common pathogenic variant in the northern European population.1,2 1. Hicks et al. Brain. 2011 Jan;134(Pt 1):171-82. 2. Sarkozy et … (more) The c.191dupA ANO5 variant is a common pathogenic variant in the northern European population.1,2 1. Hicks et al. Brain. 2011 Jan;134(Pt 1):171-82. 2. Sarkozy et al. Hum Mutat. 2013 Aug;34(8):1111-8. AKT 4-29-16 (less)	Publications: PubMed (4) PubMed: 23757202‚ 20096397‚ 21186264‚ 23606453 Other databases http://geneticslab.emory.edu/emv… http://geneticslab.emory.edu/emvclass/emvclass.php?approved_symbol=ANO5 Comment: The c.191dupA ANO5 variant is a common pathogenic variant in the northern European population.1,2 1. Hicks et al. Brain. 2011 Jan;134(Pt 1):171-82. 2. Sarkozy et … (more) The c.191dupA ANO5 variant is a common pathogenic variant in the northern European population.1,2 1. Hicks et al. Brain. 2011 Jan;134(Pt 1):171-82. 2. Sarkozy et al. Hum Mutat. 2013 Aug;34(8):1111-8. AKT 4-29-16 (less) Number of individuals with the variant: 98 Sex: mixed
Pathogenic (Jan 01, 2016)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Gnathodiaphyseal dysplasia Affected status: yes Allele origin: unknown	Centre for Mendelian Genomics, University Medical Centre Ljubljana Accession: SCV001366446.2 First in ClinVar: Jul 04, 2020 Last updated: Jul 04, 2020	Comment: This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM3,PM4,PP4,PP3.
Pathogenic (May 04, 2022)	criteria provided, single submitter (Mendelics Assertion Criteria 2019) Method: clinical testing	Gnathodiaphyseal dysplasia Affected status: unknown Allele origin: germline	Mendelics Accession: SCV002518471.1 First in ClinVar: May 28, 2022 Last updated: May 28, 2022
Pathogenic (Aug 25, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Autosomal recessive limb-girdle muscular dystrophy type 2L Affected status: yes Allele origin: germline	MGZ Medical Genetics Center Accession: SCV002581828.1 First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 Comment: ACMG criteria applied: PVS1, PS4_MOD, PM3, PP1	Number of individuals with the variant: 13 Sex: male
Pathogenic (Jul 29, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Autosomal recessive limb-girdle muscular dystrophy type 2L Affected status: yes Allele origin: germline	Genetics and Molecular Pathology, SA Pathology Additional submitter: Shariant Australia, Australian Genomics Accession: SCV002761826.1 First in ClinVar: Dec 17, 2022 Last updated: Dec 17, 2022
Pathogenic (Jan 29, 2021)	criteria provided, single submitter (Classification criteria August 2017) Method: clinical testing	Autosomal recessive limb-girdle muscular dystrophy type 2L (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München Accession: SCV001149685.2 First in ClinVar: Feb 03, 2020 Last updated: Dec 24, 2022	Number of individuals with the variant: 1 Clinical Features: Myopathy (present) , Frequent falls (present) , Proximal muscle weakness (present)
Pathogenic (Feb 23, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Autosomal recessive limb-girdle muscular dystrophy type 2L Affected status: yes Allele origin: unknown	3billion Accession: SCV003841578.1 First in ClinVar: Mar 18, 2023 Last updated: Mar 18, 2023	Publications: PubMed (8) PubMed: 23041008‚ 22402862‚ 27911336‚ 26886200‚ 22980763‚ 20096397‚ 25891276‚ 23606453 Comment: The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.106%). This variant was predicted to result in … (more) The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.106%). This variant was predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least 4 similarly affected unrelated individuals (PMID: 22402862, 22980763, 23041008, 23606453, 25891276, 26886200, 27911336). The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000002164 / PMID: 20096397 / 3billion dataset). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. (less) Clinical Features: Elevated circulating creatine kinase concentration (present) , Myalgia (present) , Calf muscle hypertrophy (present)
Pathogenic (Nov 03, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: not provided Allele origin: germline	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden Accession: SCV002009730.3 First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023
Pathogenic (Jun 08, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Revvity Omics, Revvity Accession: SCV002017103.3 First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024
Pathogenic (Jul 12, 2017)	criteria provided, single submitter (Athena Diagnostics Criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Athena Diagnostics Accession: SCV000255643.4 First in ClinVar: Oct 19, 2015 Last updated: Feb 15, 2018	Publications: PubMed (16) PubMed: 23607914‚ 24232312‚ 22499103‚ 25891276‚ 22194990‚ 20096397‚ 21186264‚ 22336395‚ 22402862‚ 21820307‚ 22980763‚ 23041008‚ 24022920‚ 27708273‚ 23606453‚ 24843231
Pathogenic (Aug 29, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 09 May 2019) Method: clinical testing	ANO5-Related Disorders Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000914503.1 First in ClinVar: May 27, 2019 Last updated: May 27, 2019	Publications: PubMed (7) PubMed: 22742934‚ 23606453‚ 23607914‚ 22402862‚ 20096397‚ 21186264‚ 21739273 Comment: The ANO5 c.191dupA (p.Asn64LysfsTer15) variant results in a frameshift and is predicted to result in premature termination of the protein. Across a selection of the … (more) The ANO5 c.191dupA (p.Asn64LysfsTer15) variant results in a frameshift and is predicted to result in premature termination of the protein. Across a selection of the available literature, the p.Asn64LysfsTer15 variant has been identified in at least 78 individuals with limb-girdle muscular dystrophy including 36 homozygotes and 42 compound heterozygotes; in two individuals with hyperCKemia in a compound heterozygous state; two individuals with myopathy, one in a homozygous state and one in a compound heterozygous state; three siblings with Miyoshi myopathy in a homozygous state; and eight individuals in a heterozygous state (Bolduc et al. 2010; Hicks et al. 2011; Deschauer et al. 2011; PenttilÃ¤et al. 2012; Magri et al. 2012; Sarkozy et al, 2013; Van der Kooi et al. 2013). The p.Asn64LysfsTer15 variant is reported as being one of the most common ANO5 pathogenic variants found in Northern European populations (Hicks et al., 2011). The p.Asn64LysfsTer15 variant has been reported in three of at least 500 control subjects and is reported at a frequency of 0.002186 in the population of the Exome Sequencing Project. Based on the potential impact of frameshift variants and collective evidence from the literature, the p.Asn64LysfsTer15 variant is classified as pathogenic for ANO5-Related Disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
Pathogenic (Oct 23, 2020)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided (Autosomal unknown) Affected status: yes Allele origin: germline	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen Accession: SCV001448041.1 First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020	Clinical Features: Myopathy (present) Sex: male
Pathogenic (Oct 19, 2022)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	Autosomal recessive limb-girdle muscular dystrophy Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV002600595.1 First in ClinVar: Nov 19, 2022 Last updated: Nov 19, 2022	Publications: PubMed (4) PubMed: 25891276‚ 20096397‚ 9673985‚ 28187523 Comment: Variant summary: ANO5 c.191dupA (p.Asn64LysfsX15) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more) Variant summary: ANO5 c.191dupA (p.Asn64LysfsX15) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic within ClinVar (e.g. c.304_308del [p.Lys102fs], c.835C>T [p.Arg279Ter]). The variant allele was found at a frequency of 0.0011 in 249002 control chromosomes in the gnomAD database, including 2 homozygotes. This frequency is not significantly higher than expected for a pathogenic variant in ANO5 causing Limb-Girdle Muscular Dystrophy, Autosomal Recessive (0.0011 vs 0.0047), allowing no conclusion about variant significance. c.191dupA has been reported in the literature as a biallelic genotype in multiple individuals affected with Limb-Girdle Muscular Dystrophy, Miyoshi Muscular Dystrophy, and Symptomatic/Asymptomatic HyperCKemia among other muscular disorders (e.g. Bolduc_2010, Savarese_2015, Papadopoulos_2017). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Twenty-one ClinVar submitters have assessed the variant since 2014: one classified the variant as likely benign, one as likely pathogenic, and nineteen as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
Pathogenic (Aug 21, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Gnathodiaphyseal dysplasia Autosomal recessive limb-girdle muscular dystrophy type 2L Miyoshi muscular dystrophy 3 Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002801207.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Pathogenic (Dec 17, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: yes Allele origin: germline	Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital Accession: SCV002818219.1 First in ClinVar: Jan 07, 2023 Last updated: Jan 07, 2023
Pathogenic (Mar 31, 2022)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000329066.8 First in ClinVar: Dec 06, 2016 Last updated: Mar 04, 2023	Comment: Observed in the heterozygous state without a second variant in multiple individuals from a cohort of patients with limb-girdle muscular dystrophy and/or Miyoshi muscular dystrophy … (more) Observed in the heterozygous state without a second variant in multiple individuals from a cohort of patients with limb-girdle muscular dystrophy and/or Miyoshi muscular dystrophy type 3 and related disorders; however, patient-specific data was not provided (Savarese et al., 2015; Sarkozy et al., 2013); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 26810512, 25864073, 27142102, 26911675, 27708273, 24022920, 24843231, 23530687, 24232312, 21739273, 23607914, 22336395, 20096397, 23041008, 21186264, 26886200, 26913919, 30564623, 29794579, 30919934, 31395899, 31862442, 32403337, 31980526, 32399949, 31127727, 25891276, 34313030, 33837115, 23606453, 34106991, 31589614, 29417091, 32367299, 33258288, 25214167, 32819793, 33726816, 32528171, 32925086) (less)
Pathogenic (Aug 02, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	ANO5-related muscular dystrophy Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV004041208.1 First in ClinVar: Oct 07, 2023 Last updated: Oct 07, 2023
Pathogenic (May 23, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Not provided Affected status: unknown Allele origin: germline	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV001714372.2 First in ClinVar: Jun 15, 2021 Last updated: Jan 26, 2024	Publications: PubMed (2) PubMed: 20096397‚ 21186264 Comment: PP1, PP5, PM3, PS4, PVS1 Number of individuals with the variant: 9
Pathogenic (Jan 30, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Autosomal recessive limb-girdle muscular dystrophy type 2L Gnathodiaphyseal dysplasia Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000645880.9 First in ClinVar: Dec 26, 2017 Last updated: Feb 28, 2024	Publications: PubMed (8) PubMed: 28492532‚ 21186264‚ 23606453‚ 25891276‚ 30919934‚ 20096397‚ 21739273‚ 23607914 Comment: This sequence change creates a premature translational stop signal (p.Asn64Lysfs15) in the ANO5 gene. It is expected to result in an absent or disrupted protein … (more) This sequence change creates a premature translational stop signal (p.Asn64Lysfs15) in the ANO5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ANO5 are known to be pathogenic (PMID: 21186264, 23606453, 25891276, 30919934). This variant is present in population databases (rs575136178, gnomAD 0.2%), including at least one homozygous and/or hemizygous individual. This premature translational stop signal has been observed in individuals with autosomal recessive limb-girdle muscular dystrophy 2L (LGMD2L) and ANO5-related conditions (PMID: 20096397, 21186264, 21739273, 23606453, 23607914, 25891276). It is commonly reported in individuals of Northern European ancestry (PMID: 20096397, 21186264, 21739273, 23607914). ClinVar contains an entry for this variant (Variation ID: 2164). For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Feb 05, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Autosomal recessive limb-girdle muscular dystrophy (Autosomal recessive inheritance) Affected status: unknown Allele origin: germline	Molecular Genetics, Royal Melbourne Hospital Additional submitter: Shariant Australia, Australian Genomics Accession: SCV002503669.2 First in ClinVar: Apr 28, 2022 Last updated: Apr 15, 2024	Publications: PubMed (3) PubMed: 21186264‚ 25891276‚ 27708273 Comment: This sequence change in ANO5 is a frameshift variant predicted to cause a premature stop codon, p.(Asn64Lysfs15), in biologically relevant exon 5/22 leading to nonsense-mediated … (more) This sequence change in ANO5 is a frameshift variant predicted to cause a premature stop codon, p.(Asn64Lysfs15), in biologically relevant exon 5/22 leading to nonsense-mediated decay in a gene in which loss-of-function is an established disease mechanism. The highest population minor allele frequency in the population database gnomAD v4.0 is 0.27% (3,169/1,176,516 alleles, 4 homozygotes) in the European (non-Finnish) population. The variant is recognised to be a Northern European founder mutation for ANO5-related muscle disease and has been detected in the homozygous and compound heterozygous state in multiple affected individuals (PMID: 21186264, 27708273, 25891276). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.6.1, this variant is classified as PATHOGENIC. Following criteria are met: PVS1, PM3_VeryStrong. (less)
Pathogenic (Aug 16, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Autosomal recessive limb-girdle muscular dystrophy type 2L (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Department of Human Genetics, Hannover Medical School Accession: SCV005196403.1 First in ClinVar: Aug 18, 2024 Last updated: Aug 18, 2024	Clinical Features: Hyporeflexia (present) , Elevated circulating creatine kinase concentration (present) , Myalgia (present) , EMG: myopathic abnormalities (present) , Calf muscle pseudohypertrophy (present) , Distal lower … (more) Hyporeflexia (present) , Elevated circulating creatine kinase concentration (present) , Myalgia (present) , EMG: myopathic abnormalities (present) , Calf muscle pseudohypertrophy (present) , Distal lower limb muscle weakness (present) (less)
Pathogenic (Feb 01, 2024)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV001245645.26 First in ClinVar: May 12, 2020 Last updated: Oct 20, 2024	Comment: ANO5: PM3:Very Strong, PVS1, PM2:Supporting Number of individuals with the variant: 23
Pathogenic (Nov 29, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Autosomal recessive limb-girdle muscular dystrophy type 2L Affected status: yes Allele origin: germline	Institute of Immunology and Genetics Kaiserslautern Accession: SCV005382149.1 First in ClinVar: Oct 26, 2024 Last updated: Oct 26, 2024	Comment: ACMG Criteria: PVS1, PS4, PM3, PP5; Variant was found in heterozygous state. Clinical Features: Myopathy (present) , Mildly elevated creatine kinase (present) , Peripheral neuropathy (present) , Increased muscle fatiguability (present)
Pathogenic (Mar 20, 2012)	no assertion criteria provided Method: literature only	MIYOSHI MUSCULAR DYSTROPHY 3 Affected status: not provided Allele origin: germline	OMIM Accession: SCV000022405.5 First in ClinVar: Apr 04, 2013 Last updated: Sep 28, 2018	Publications: PubMed (3) PubMed: 20096397‚ 9673985‚ 22402862 Comment on evidence: Bolduc et al. (2010) found homozygosity for a 1-bp duplication (191dupA) in exon 5 of the ANO5 gene in a Dutch family with Miyoshi muscular … (more) Bolduc et al. (2010) found homozygosity for a 1-bp duplication (191dupA) in exon 5 of the ANO5 gene in a Dutch family with Miyoshi muscular dystrophy-3 (MMD3; 613319) originally reported by Linssen et al. (1998) as family IV. The 191dupA mutation resulted in a frameshift and premature termination, consistent with a loss of function. It was absent in 210 French Canadian and 152 CEPH control chromosomes, but was identified in 1 of 100 UK and 2 of 210 Dutch control chromosomes. In a 63-year-old French Canadian woman with autosomal recessive limb-girdle muscular dystrophy type 2L (LGMDR12; 611307) and mild distal limb weakness, Bolduc et al. (2010) identified compound heterozygosity for 191dupA and a 692G-T transversion in exon 8 of the ANO5 gene, resulting in a gly231-to-val substitution (G231V; 608662.0005) in the intracellular N-terminal tail. The patient had late-onset asymmetric proximal upper limb and iliopsoas weakness and distal upper and lower limb weakness, as well as increased serum creatine kinase. Bolduc et al. (2010) noted that the phenotype overlapped between LGMD2L and Miyoshi myopathy. Among 25 patients, mostly of Finnish descent, with variable muscle disorders due to recessive ANO5 mutations, Penttila et al. (2012) found that 191dupA was the second most common mutation, occurring in the heterozygous state with another ANO5 mutation in 10 patients. The phenotype was highly variable: female mutation carriers had a mild disorder with myalgia and/or calf hypertrophy and hyperCKemia, whereas men with the mutation showed distal lower limb weakness or proximal upper and lower limb muscle weakness. The findings indicated that this mutation can be associated with a variety of muscle phenotypes. Two Spanish brothers with LGMD2L were compound heterozygous for 191dupA and G231V. (less)
Pathogenic (Mar 20, 2012)	no assertion criteria provided Method: literature only	MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 12 Affected status: not provided Allele origin: germline	OMIM Accession: SCV000809056.1 First in ClinVar: Sep 28, 2018 Last updated: Sep 28, 2018	Publications: PubMed (3) PubMed: 20096397‚ 9673985‚ 22402862 Comment on evidence: Bolduc et al. (2010) found homozygosity for a 1-bp duplication (191dupA) in exon 5 of the ANO5 gene in a Dutch family with Miyoshi muscular … (more) Bolduc et al. (2010) found homozygosity for a 1-bp duplication (191dupA) in exon 5 of the ANO5 gene in a Dutch family with Miyoshi muscular dystrophy-3 (MMD3; 613319) originally reported by Linssen et al. (1998) as family IV. The 191dupA mutation resulted in a frameshift and premature termination, consistent with a loss of function. It was absent in 210 French Canadian and 152 CEPH control chromosomes, but was identified in 1 of 100 UK and 2 of 210 Dutch control chromosomes. In a 63-year-old French Canadian woman with autosomal recessive limb-girdle muscular dystrophy type 2L (LGMDR12; 611307) and mild distal limb weakness, Bolduc et al. (2010) identified compound heterozygosity for 191dupA and a 692G-T transversion in exon 8 of the ANO5 gene, resulting in a gly231-to-val substitution (G231V; 608662.0005) in the intracellular N-terminal tail. The patient had late-onset asymmetric proximal upper limb and iliopsoas weakness and distal upper and lower limb weakness, as well as increased serum creatine kinase. Bolduc et al. (2010) noted that the phenotype overlapped between LGMD2L and Miyoshi myopathy. Among 25 patients, mostly of Finnish descent, with variable muscle disorders due to recessive ANO5 mutations, Penttila et al. (2012) found that 191dupA was the second most common mutation, occurring in the heterozygous state with another ANO5 mutation in 10 patients. The phenotype was highly variable: female mutation carriers had a mild disorder with myalgia and/or calf hypertrophy and hyperCKemia, whereas men with the mutation showed distal lower limb weakness or proximal upper and lower limb muscle weakness. The findings indicated that this mutation can be associated with a variety of muscle phenotypes. Two Spanish brothers with LGMD2L were compound heterozygous for 191dupA and G231V. (less)
Likely benign (Jan 01, 2019)	no assertion criteria provided Method: clinical testing	Intellectual disability Affected status: yes Allele origin: inherited	Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille Accession: SCV001427407.1 First in ClinVar: Aug 15, 2020 Last updated: Aug 15, 2020	Publications: PubMed (1) PubMed: 25741868
Pathogenic (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) Study: VKGL Data-share Consensus Accession: SCV001797445.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021
Pathogenic (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001974455.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021
Pathogenic (Dec 06, 2023)	no assertion criteria provided Method: clinical testing	ANO5-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004109121.3 First in ClinVar: Nov 20, 2023 Last updated: Oct 08, 2024	Comment: The ANO5 c.191dupA variant is predicted to result in a frameshift and premature protein termination (p.Asn64Lysfs15). This variant in the homozygous or compound heterozygous state … (more) The ANO5 c.191dupA variant is predicted to result in a frameshift and premature protein termination (p.Asn64Lysfs15). This variant in the homozygous or compound heterozygous state has been reported in patients with autosomal recessive proximal limb-girdle muscular dystrophy or Miyoshi-like myopathy (Bolduc et al. 2010. PubMed ID: 20096397; Hicks et al. 2011. PubMed ID: 21186264; Bouquet et al. 2012. PubMed ID: 22336395). This variant is reported in 0.21% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Frameshift variants in ANO5 are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
Pathogenic (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Clinical Genetics, Academic Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001925201.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021
Pathogenic (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, University Medical Center Utrecht Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001927435.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021
Pathogenic (Aug 23, 2021)	no assertion criteria provided Method: clinical testing	Autosomal recessive limb-girdle muscular dystrophy type 2L Affected status: yes Allele origin: germline	Clinical Genetics Laboratory, University Hospital Schleswig-Holstein Accession: SCV002011774.1 First in ClinVar: Nov 06, 2021 Last updated: Nov 06, 2021
not provided (-)	no classification provided Method: phenotyping only	ANO5-related disorder Affected status: unknown Allele origin: unknown	GenomeConnect - Invitae Patient Insights Network Accession: SCV001749728.1 First in ClinVar: Jul 18, 2021 Last updated: Jul 18, 2021	Comment: Variant reported in multiple Invitae PIN participants. Variant interpreted as Pathogenic and reported most recently on 10/28/2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are … (more) Variant reported in multiple Invitae PIN participants. Variant interpreted as Pathogenic and reported most recently on 10/28/2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. (less) Observation 1: Number of individuals with the variant: 1 Clinical Features: Myopia (present) , Abnormal skeletal muscle morphology (present) , Abnormal muscle physiology (present) , Abnormality of the musculature of the limbs (present) , Maternal teratogenic … (more) Myopia (present) , Abnormal skeletal muscle morphology (present) , Abnormal muscle physiology (present) , Abnormality of the musculature of the limbs (present) , Maternal teratogenic exposure (present) (less) Indication for testing: Diagnostic\|Family Testing Age: 60-69 years Sex: male Testing laboratory: Invitae Date variant was reported to submitter: 2019-11-11 Testing laboratory interpretation: Pathogenic Observation 2: Number of individuals with the variant: 1 Clinical Features: Autoimmunity (present) , Abnormal stomach morphology (present) , Abnormal muscle physiology (present) , Abnormality of the somatic nervous system (present) , Hyperthyroidism (present) , Movement … (more) Autoimmunity (present) , Abnormal stomach morphology (present) , Abnormal muscle physiology (present) , Abnormality of the somatic nervous system (present) , Hyperthyroidism (present) , Movement disorder (present) (less) Indication for testing: Diagnostic Age: 20-29 years Sex: female Testing laboratory: Invitae Date variant was reported to submitter: 2020-01-14 Testing laboratory interpretation: Pathogenic Observation 3: Number of individuals with the variant: 1 Clinical Features: Myopia (present) , Feeding difficulties (present) , Abnormal stomach morphology (present) , Abnormal curvature of the vertebral column (present) , Anxiety (present) , Depression (present) … (more) Myopia (present) , Feeding difficulties (present) , Abnormal stomach morphology (present) , Abnormal curvature of the vertebral column (present) , Anxiety (present) , Depression (present) , Motor stereotypies (present) (less) Indication for testing: Diagnostic Age: 30-39 years Sex: female Testing laboratory: Invitae Date variant was reported to submitter: 2020-10-28 Testing laboratory interpretation: Pathogenic
not provided (-)	no classification provided Method: not provided	not provided Affected status: not provided Allele origin: unknown	ANO5 @LOVD Accession: SCV000172417.1 First in ClinVar: Jul 23, 2014 Last updated: Jul 23, 2014
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Comment:

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.106%). This variant was predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least 4 similarly affected unrelated individuals (PMID: 22402862, 22980763, 23041008, 23606453, 25891276, 26886200, 27911336). The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000002164 / PMID: 20096397 / 3billion dataset). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.

Comment:

The ANO5 c.191dupA (p.Asn64LysfsTer15) variant results in a frameshift and is predicted to result in premature termination of the protein. Across a selection of the available literature, the p.Asn64LysfsTer15 variant has been identified in at least 78 individuals with limb-girdle muscular dystrophy including 36 homozygotes and 42 compound heterozygotes; in two individuals with hyperCKemia in a compound heterozygous state; two individuals with myopathy, one in a homozygous state and one in a compound heterozygous state; three siblings with Miyoshi myopathy in a homozygous state; and eight individuals in a heterozygous state (Bolduc et al. 2010; Hicks et al. 2011; Deschauer et al. 2011; PenttilÃ¤et al. 2012; Magri et al. 2012; Sarkozy et al, 2013; Van der Kooi et al. 2013). The p.Asn64LysfsTer15 variant is reported as being one of the most common ANO5 pathogenic variants found in Northern European populations (Hicks et al., 2011). The p.Asn64LysfsTer15 variant has been reported in three of at least 500 control subjects and is reported at a frequency of 0.002186 in the population of the Exome Sequencing Project. Based on the potential impact of frameshift variants and collective evidence from the literature, the p.Asn64LysfsTer15 variant is classified as pathogenic for ANO5-Related Disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

Comment:

Variant summary: ANO5 c.191dupA (p.Asn64LysfsX15) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic within ClinVar (e.g. c.304_308del [p.Lys102fs], c.835C>T [p.Arg279Ter]). The variant allele was found at a frequency of 0.0011 in 249002 control chromosomes in the gnomAD database, including 2 homozygotes. This frequency is not significantly higher than expected for a pathogenic variant in ANO5 causing Limb-Girdle Muscular Dystrophy, Autosomal Recessive (0.0011 vs 0.0047), allowing no conclusion about variant significance. c.191dupA has been reported in the literature as a biallelic genotype in multiple individuals affected with Limb-Girdle Muscular Dystrophy, Miyoshi Muscular Dystrophy, and Symptomatic/Asymptomatic HyperCKemia among other muscular disorders (e.g. Bolduc_2010, Savarese_2015, Papadopoulos_2017). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Twenty-one ClinVar submitters have assessed the variant since 2014: one classified the variant as likely benign, one as likely pathogenic, and nineteen as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

Comment:

Observed in the heterozygous state without a second variant in multiple individuals from a cohort of patients with limb-girdle muscular dystrophy and/or Miyoshi muscular dystrophy type 3 and related disorders; however, patient-specific data was not provided (Savarese et al., 2015; Sarkozy et al., 2013); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 26810512, 25864073, 27142102, 26911675, 27708273, 24022920, 24843231, 23530687, 24232312, 21739273, 23607914, 22336395, 20096397, 23041008, 21186264, 26886200, 26913919, 30564623, 29794579, 30919934, 31395899, 31862442, 32403337, 31980526, 32399949, 31127727, 25891276, 34313030, 33837115, 23606453, 34106991, 31589614, 29417091, 32367299, 33258288, 25214167, 32819793, 33726816, 32528171, 32925086)

Comment:

This sequence change creates a premature translational stop signal (p.Asn64Lysfs*15) in the ANO5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ANO5 are known to be pathogenic (PMID: 21186264, 23606453, 25891276, 30919934). This variant is present in population databases (rs575136178, gnomAD 0.2%), including at least one homozygous and/or hemizygous individual. This premature translational stop signal has been observed in individuals with autosomal recessive limb-girdle muscular dystrophy 2L (LGMD2L) and ANO5-related conditions (PMID: 20096397, 21186264, 21739273, 23606453, 23607914, 25891276). It is commonly reported in individuals of Northern European ancestry (PMID: 20096397, 21186264, 21739273, 23607914). ClinVar contains an entry for this variant (Variation ID: 2164). For these reasons, this variant has been classified as Pathogenic.

Comment:

This sequence change in ANO5 is a frameshift variant predicted to cause a premature stop codon, p.(Asn64Lysfs*15), in biologically relevant exon 5/22 leading to nonsense-mediated decay in a gene in which loss-of-function is an established disease mechanism. The highest population minor allele frequency in the population database gnomAD v4.0 is 0.27% (3,169/1,176,516 alleles, 4 homozygotes) in the European (non-Finnish) population. The variant is recognised to be a Northern European founder mutation for ANO5-related muscle disease and has been detected in the homozygous and compound heterozygous state in multiple affected individuals (PMID: 21186264, 27708273, 25891276). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.6.1, this variant is classified as PATHOGENIC. Following criteria are met: PVS1, PM3_VeryStrong.

Comment:

The ANO5 c.191dupA variant is predicted to result in a frameshift and premature protein termination (p.Asn64Lysfs*15). This variant in the homozygous or compound heterozygous state has been reported in patients with autosomal recessive proximal limb-girdle muscular dystrophy or Miyoshi-like myopathy (Bolduc et al. 2010. PubMed ID: 20096397; Hicks et al. 2011. PubMed ID: 21186264; Bouquet et al. 2012. PubMed ID: 22336395). This variant is reported in 0.21% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Frameshift variants in ANO5 are expected to be pathogenic. This variant is interpreted as pathogenic.

Comment:

Variant reported in multiple Invitae PIN participants. Variant interpreted as Pathogenic and reported most recently on 10/28/2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Autosomal recessive limb-girdle and Miyoshi muscular dystrophies in the Netherlands: The clinical and molecular spectrum of 244 patients.	Ten Dam L	Clinical genetics	2019	PMID: 30919934
Hyperckemia and myalgia are common presentations of anoctamin-5-related myopathy in French patients.	Papadopoulos C	Muscle & nerve	2017	PMID: 28187523
The sensitivity of exome sequencing in identifying pathogenic mutations for LGMD in the United States.	Reddy HM	Journal of human genetics	2017	PMID: 27708273
Decreased Aerobic Capacity in ANO5-Muscular Dystrophy.	Ylikallio E	Journal of neuromuscular diseases	2016	PMID: 27911336
Utility of a next-generation sequencing-based gene panel investigation in German patients with genetically unclassified limb-girdle muscular dystrophy.	Kuhn M	Journal of neurology	2016	PMID: 26886200
Next generation sequencing on patients with LGMD and nonspecific myopathies: Findings associated with ANO5 mutations.	Savarese M	Neuromuscular disorders : NMD	2015	PMID: 25891276
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.	Richards S	Genetics in medicine : official journal of the American College of Medical Genetics	2015	PMID: 25741868
Limb girdle muscular dystrophy type 2L presenting as necrotizing myopathy.	Schneider I	Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology	2014	PMID: 24843231
Macular dystrophy presenting in one of two siblings with limb-girdle muscular dystrophy type 2L due to mutation of ANO5.	Vaz-Pereira S	Eye (London, England)	2014	PMID: 24232312
A case of progressive quadriceps weakness and elevated creatine kinase level mimicking inclusion body myositis.	Leung DG	Arthritis care & research	2014	PMID: 24022920
ANO5 mutations in the Dutch limb girdle muscular dystrophy population.	van der Kooi AJ	Neuromuscular disorders : NMD	2013	PMID: 23607914
ANO5 gene analysis in a large cohort of patients with anoctaminopathy: confirmation of male prevalence and high occurrence of the common exon 5 gene mutation.	Sarkozy A	Human mutation	2013	PMID: 23606453
Dilated cardiomyopathy in patients with mutations in anoctamin 5.	Wahbi K	International journal of cardiology	2013	PMID: 23041008
Muscle MRI findings in limb girdle muscular dystrophy type 2L.	Sarkozy A	Neuromuscular disorders : NMD	2012	PMID: 22980763
Frequency and characterisation of anoctamin 5 mutations in a cohort of Italian limb-girdle muscular dystrophy patients.	Magri F	Neuromuscular disorders : NMD	2012	PMID: 22742934
Novel ANO5 mutations causing hyper-CK-emia, limb girdle muscular weakness and Miyoshi type of muscular dystrophy.	Schessl J	Muscle & nerve	2012	PMID: 22499103
Eight new mutations and the expanding phenotype variability in muscular dystrophy caused by ANO5.	Penttilä S	Neurology	2012	PMID: 22402862
Miyoshi-like distal myopathy with mutations in anoctamin 5 gene.	Bouquet F	Revue neurologique	2012	PMID: 22336395
Amyloidosis and exercise intolerance in ANO5 muscular dystrophy.	Milone M	Neuromuscular disorders : NMD	2012	PMID: 21820307
Comparison of dysferlin expression in human skeletal muscle with that in monocytes for the diagnosis of dysferlin myopathy.	Gallardo E	PloS one	2011	PMID: 22194990
[Muscular dystrophy due to mutations in anoctamin 5: clinical and molecular genetic findings].	Deschauer M	Der Nervenarzt	2011	PMID: 21739273
A founder mutation in Anoctamin 5 is a major cause of limb-girdle muscular dystrophy.	Hicks D	Brain : a journal of neurology	2011	PMID: 21186264
Recessive mutations in the putative calcium-activated chloride channel Anoctamin 5 cause proximal LGMD2L and distal MMD3 muscular dystrophies.	Bolduc V	American journal of human genetics	2010	PMID: 20096397
Genetic heterogeneity in Miyoshi-type distal muscular dystrophy.	Linssen WH	Neuromuscular disorders : NMD	1998	PMID: 9673985
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Text-mined citations for rs137854521 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 19, 2024

ClinVar Genomic variation as it relates to human health

NM_213599.3(ANO5):c.191dup (p.Asn64fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs137854521 ...