ClinVar Genomic variation as it relates to human health
NM_001159699.2(FHL1):c.871G>A (p.Asp291Asn)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001159699.2(FHL1):c.871G>A (p.Asp291Asn)
Variation ID: 239013 Accession: VCV000239013.33
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: Xq26.3 X: 136210005 (GRCh38) [ NCBI UCSC ] X: 135292164 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Mar 8, 2017 May 1, 2024 Feb 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001159699.2:c.871G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001153171.1:p.Asp291Asn missense NM_001159702.3:c.*51G>A MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
3 prime UTR NM_001159700.2:c.823G>A NP_001153172.1:p.Asp275Asn missense NM_001159701.2:c.910G>A NP_001153173.1:p.Asp304Asn missense NM_001159703.2:c.*51G>A 3 prime UTR NM_001159704.1:c.823G>A NP_001153176.1:p.Asp275Asn missense NM_001167819.1:c.823G>A NP_001161291.1:p.Asp275Asn missense NM_001330659.2:c.*51G>A 3 prime UTR NM_001369326.1:c.*51G>A 3 prime UTR NM_001369327.2:c.*51G>A 3 prime UTR NM_001369328.1:c.*51G>A 3 prime UTR NM_001369329.1:c.823G>A NP_001356258.1:p.Asp275Asn missense NM_001369330.1:c.823G>A NP_001356259.1:p.Asp275Asn missense NM_001369331.1:c.823G>A NP_001356260.1:p.Asp275Asn missense NM_001449.5:c.823G>A NP_001440.2:p.Asp275Asn missense NR_027621.2:n.1234G>A non-coding transcript variant NC_000023.11:g.136210005G>A NC_000023.10:g.135292164G>A NG_015895.1:g.67606G>A LRG_739:g.67606G>A LRG_739t1:c.871G>A LRG_739p1:p.Asp291Asn LRG_739t2:c.*51G>A - Protein change
- D275N, D291N, D304N
- Other names
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- Canonical SPDI
- NC_000023.11:136210004:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe 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.
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0.00477 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.00477
1000 Genomes Project 30x 0.00520
The Genome Aggregation Database (gnomAD), exomes 0.01086
Trans-Omics for Precision Medicine (TOPMed) 0.01100
Exome Aggregation Consortium (ExAC) 0.01128
The Genome Aggregation Database (gnomAD) 0.01175
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.01306
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 | ||
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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. |
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FHL1 | - | - |
GRCh38 GRCh37 |
488 | 662 |
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. |
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Benign (1) |
criteria provided, single submitter
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Feb 1, 2024 | RCV000228514.18 | |
Benign (3) |
criteria provided, single submitter
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Aug 24, 2018 | RCV000991990.21 | |
Benign (1) |
criteria provided, single submitter
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Jan 3, 2019 | RCV002408965.9 | |
Benign (6) |
criteria provided, multiple submitters, no conflicts
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Apr 29, 2021 | RCV000296313.18 | |
Benign (1) |
criteria provided, single submitter
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Oct 19, 2023 | RCV003741168.1 |
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. |
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Benign
(Jan 03, 2019)
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criteria provided, single submitter
Method: clinical testing
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Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002676150.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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Benign
(Dec 03, 2015)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000336163.4
First in ClinVar: Dec 06, 2016 Last updated: Mar 08, 2017 |
Number of individuals with the variant: 1
Sex: mixed
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Benign
(Mar 04, 2016)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000522548.4
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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X-linked myopathy with postural muscle atrophy
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000287134.8
First in ClinVar: Jul 01, 2016 Last updated: Feb 14, 2024 |
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Benign
(Aug 24, 2018)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Athena Diagnostics
Accession: SCV001143923.1
First in ClinVar: Jan 19, 2020 Last updated: Jan 19, 2020 |
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Benign
(Apr 29, 2021)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001623250.1
First in ClinVar: May 23, 2021 Last updated: May 23, 2021 |
Comment:
Variant summary: FHL1 c.*51G>A is located in the untranslated mRNA region downstream of the termination codon. The variant allele was found at a frequency of … (more)
Variant summary: FHL1 c.*51G>A is located in the untranslated mRNA region downstream of the termination codon. The variant allele was found at a frequency of 0.011 in 183528 control chromosomes in the gnomAD database, including 17 homozygotes. The observed variant frequency is approximately 28 fold of the estimated maximal expected allele frequency for a pathogenic variant in FHL1 causing Emery-Dreifuss Muscular Dystrophy phenotype (0.00039), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.*51G>A in individuals affected with Emery-Dreifuss Muscular Dystrophy and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign. (less)
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Benign
(Oct 19, 2023)
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criteria provided, single submitter
Method: clinical testing
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Familial hemophagocytic lymphohistiocytosis type 1
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001157535.6
First in ClinVar: Feb 10, 2020 Last updated: Feb 20, 2024 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001800519.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001921766.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001930630.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001952924.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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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: SCV001965230.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Homozygous truncating mutation in NRAP gene identified by whole exome sequencing in a patient with dilated cardiomyopathy. | Truszkowska GT | Scientific reports | 2017 | PMID: 28611399 |
Exome sequencing identifies variants in two genes encoding the LIM-proteins NRAP and FHL1 in an Italian patient with BAG3 myofibrillar myopathy. | D'Avila F | Journal of muscle research and cell motility | 2016 | PMID: 27443559 |
Evidence for FHL1 as a novel disease gene for isolated hypertrophic cardiomyopathy. | Friedrich FW | Human molecular genetics | 2012 | PMID: 22523091 |
Consequences of mutations within the C terminus of the FHL1 gene. | Schoser B | Neurology | 2009 | PMID: 19687455 |
A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation. | Tarpey PS | Nature genetics | 2009 | PMID: 19377476 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=FHL1 | - | - | - | - |
Text-mined citations for rs151315725 ...
HelpRecord last updated Sep 01, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.