ClinVar Genomic variation as it relates to human health
NM_001201543.2(FAM161A):c.1309A>T (p.Arg437Ter)
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_001201543.2(FAM161A):c.1309A>T (p.Arg437Ter)
Variation ID: 36 Accession: VCV000000036.62
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2p15 2: 61839695 (GRCh38) [ NCBI UCSC ] 2: 62066830 (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 Apr 4, 2013 Oct 8, 2024 Mar 25, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001201543.2:c.1309A>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001188472.1:p.Arg437Ter nonsense NM_032180.3:c.1309A>T NP_115556.2:p.Arg437Ter nonsense NR_037710.2:n.1272A>T non-coding transcript variant NC_000002.12:g.61839695T>A NC_000002.11:g.62066830T>A NG_028125.1:g.19449A>T - Protein change
- R437*
- Other names
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- Canonical SPDI
- NC_000002.12:61839694:T: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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0.00020 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00016
1000 Genomes Project 0.00020
Exome Aggregation Consortium (ExAC) 0.00026
The Genome Aggregation Database (gnomAD), exomes 0.00028
The Genome Aggregation Database (gnomAD) 0.00030
Trans-Omics for Precision Medicine (TOPMed) 0.00032
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00042
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
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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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FAM161A | - | - |
GRCh38 GRCh37 |
780 | 873 |
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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Pathogenic (8) |
criteria provided, multiple submitters, no conflicts
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Mar 25, 2024 | RCV000000053.23 | |
Pathogenic (8) |
criteria provided, multiple submitters, no conflicts
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Jan 31, 2024 | RCV000153226.45 | |
Pathogenic (1) |
no assertion criteria provided
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Sep 1, 2016 | RCV000678572.8 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Apr 1, 2021 | RCV000778621.11 | |
Pathogenic (2) |
criteria provided, single submitter
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Jun 16, 2019 | RCV000787604.5 |
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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Pathogenic
(Sep 19, 2017)
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criteria provided, single submitter
Method: clinical testing
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Retinitis pigmentosa
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000914934.1
First in ClinVar: May 27, 2019 Last updated: May 27, 2019 |
Comment:
The FAM161A c.1309A>T (p.Arg437Ter) variant has been reported in at least five studies in 18 individuals with autosomal recessive retinitis pigmentosa, including 12 in a … (more)
The FAM161A c.1309A>T (p.Arg437Ter) variant has been reported in at least five studies in 18 individuals with autosomal recessive retinitis pigmentosa, including 12 in a homozygous state, five in a compound heterozygous state, and one in a heterozygous state in whom a second variant was not identified (Langmann et al. 2010; Wang et al. 2014; Rose et al. 2015; Van Schil et al. 2015; van Huet et al. 2015). These patients were unrelated, except for two sets of siblings who were homozygous for the p.Arg437Ter variant (Van Schil et al. 2015; Rose et al. 2015). The p.Arg437Ter variant was absent from 400 control chromosomes and is reported at a frequency of 0.00061 in the European American population of the Exome Sequencing Project. Based on the collective evidence, the p.Arg437Ter variant is classified as pathogenic for autosomal recessive retinitis pigmentosa. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
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Pathogenic
(Aug 15, 2016)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000229237.5
First in ClinVar: Jun 28, 2015 Last updated: Jul 31, 2019 |
Number of individuals with the variant: 3
Sex: mixed
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Pathogenic
(Jun 16, 2019)
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criteria provided, single submitter
Method: clinical testing
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Retinal dystrophy
Affected status: yes
Allele origin:
germline
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Blueprint Genetics
Accession: SCV001239108.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020
Comment:
My Retina Tracker patient
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Pathogenic
(Apr 08, 2021)
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criteria provided, single submitter
Method: research
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Retinitis pigmentosa 28
Affected status: yes
Allele origin:
germline
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Ocular Genomics Institute, Massachusetts Eye and Ear
Accession: SCV001573614.1
First in ClinVar: May 10, 2021 Last updated: May 10, 2021 |
Comment:
The FAM161A c.1309A>T variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we … (more)
The FAM161A c.1309A>T variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PVS1, PM2, PM3. Based on this evidence we have classified this variant as Pathogenic. (less)
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Retinitis pigmentosa 28
Affected status: yes
Allele origin:
germline
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Genomics England Pilot Project, Genomics England
Accession: SCV001760093.1
First in ClinVar: Jul 31, 2021 Last updated: Jul 31, 2021 |
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Pathogenic
(Sep 15, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001905556.1
First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
Clinical Features:
Rod-cone dystrophy (present)
Sex: male
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Pathogenic
(Apr 01, 2021)
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criteria provided, single submitter
Method: curation
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Retinitis pigmentosa
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV001950276.1
First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
Comment:
The p.Arg437Ter variant in FAM161A was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics … (more)
The p.Arg437Ter variant in FAM161A was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PVS1, PM2, PM3. Based on this evidence we have classified this variant as Pathogenic. If you have any questions about the classification please reach out to the Pierce Lab. (less)
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Pathogenic
(Jan 21, 2022)
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criteria provided, single submitter
Method: clinical testing
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Retinitis pigmentosa 28
Affected status: yes
Allele origin:
germline
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Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002556624.2
First in ClinVar: Aug 08, 2022 Last updated: Dec 17, 2022 |
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Pathogenic
(Oct 18, 2016)
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criteria provided, single submitter
Method: clinical testing
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Retinitis pigmentosa 28
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000487029.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 24, 2022 |
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Pathogenic
(Feb 09, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000329583.8
First in ClinVar: Dec 06, 2016 Last updated: Mar 04, 2023 |
Comment:
Nonsense 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 … (more)
Nonsense 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: 30718709, 25097241, 25525159, 20705278, 28559085, 26113502, 26574802, 25999674, 31589614, 34426522, 33576794) (less)
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Pathogenic
(Dec 30, 2020)
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criteria provided, single submitter
Method: clinical testing
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Retinitis pigmentosa 28
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002022279.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Jan 31, 2024)
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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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000943915.6
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg437*) in the FAM161A gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg437*) in the FAM161A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FAM161A are known to be pathogenic (PMID: 20705278, 20705279, 24651477). This variant is present in population databases (rs200691042, gnomAD 0.05%). This premature translational stop signal has been observed in individuals with FAM161A-related conditions (PMID: 20705278, 26113502, 26574802). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 36). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Mar 25, 2024)
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criteria provided, single submitter
Method: clinical testing
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Retinitis pigmentosa 28
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV001527850.2
First in ClinVar: Mar 22, 2021 Last updated: Jun 17, 2024 |
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Pathogenic
(Sep 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001246771.24
First in ClinVar: May 12, 2020 Last updated: Oct 08, 2024 |
Comment:
FAM161A: PM3:Very Strong, PVS1, PM2
Number of individuals with the variant: 4
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Pathogenic
(Oct 31, 2018)
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criteria provided, single submitter
Method: clinical testing
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Retinitis pigmentosa 28
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000894286.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
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Pathogenic
(Sep 10, 2010)
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no assertion criteria provided
Method: literature only
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RETINITIS PIGMENTOSA 28
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000020196.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
In 3 presumably unrelated German patients with retinitis pigmentosa (RP28; 606068), Langmann et al. (2010) identified homozygosity for a 1309A-T transversion in exon 3 of … (more)
In 3 presumably unrelated German patients with retinitis pigmentosa (RP28; 606068), Langmann et al. (2010) identified homozygosity for a 1309A-T transversion in exon 3 of the FAM161A gene, predicted to result in an arg437-to-ter (R437X) substitution. The mutation cosegregated with disease in the respective families and was not found in 400 ethnically matched control chromosomes. The 3 German patients shared the same FAM161A haplotype composed of 6 intragenic SNPs, suggesting that the R437X mutation originates from a common founder. (less)
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Pathogenic
(Sep 01, 2016)
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no assertion criteria provided
Method: clinical testing
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Cone-rod dystrophy
Affected status: yes
Allele origin:
inherited
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Accession: SCV000804651.2
First in ClinVar: Sep 10, 2018 Last updated: Sep 10, 2018 |
Number of individuals with the variant: 1
|
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Pathogenic
(Apr 01, 2018)
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no assertion criteria provided
Method: research
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Retinal dystrophy
Affected status: yes
Allele origin:
unknown
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Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet
Study: VeluxRD
Accession: SCV000926587.2 First in ClinVar: Jul 22, 2019 Last updated: Sep 03, 2023 |
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Pathogenic
(Apr 01, 2018)
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no assertion criteria provided
Method: research
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Retinitis pigmentosa
Affected status: yes
Allele origin:
unknown
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Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet
Study: VeluxRD
Accession: SCV000926588.2 First in ClinVar: Jul 22, 2019 Last updated: Sep 03, 2023 |
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Pathogenic
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
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Retinitis pigmentosa
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001452512.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
|
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
|
not provided
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: SCV001923391.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
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: SCV001953139.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Pathogenic
(-)
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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: SCV001974089.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 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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The importance of automation in genetic diagnosis: Lessons from analyzing an inherited retinal degeneration cohort with the Mendelian Analysis Toolkit (MATK). | Zampaglione E | Genetics in medicine : official journal of the American College of Medical Genetics | 2022 | PMID: 34906470 |
Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy. | Jespersgaard C | Scientific reports | 2019 | PMID: 30718709 |
A Nonsense Mutation in FAM161A Is a Recurrent Founder Allele in Dutch and Belgian Individuals With Autosomal Recessive Retinitis Pigmentosa. | Van Schil K | Investigative ophthalmology & visual science | 2015 | PMID: 26574802 |
Diverse clinical phenotypes associated with a nonsense mutation in FAM161A. | Rose AM | Eye (London, England) | 2015 | PMID: 26113502 |
The efficacy of microarray screening for autosomal recessive retinitis pigmentosa in routine clinical practice. | van Huet RA | Molecular vision | 2015 | PMID: 25999674 |
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 |
RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. | Xiong HY | Science (New York, N.Y.) | 2015 | PMID: 25525159 |
Dependable and efficient clinical utility of target capture-based deep sequencing in molecular diagnosis of retinitis pigmentosa. | Wang J | Investigative ophthalmology & visual science | 2014 | PMID: 25097241 |
Molecular genetics of FAM161A in North American patients with early-onset retinitis pigmentosa. | Venturini G | PloS one | 2014 | PMID: 24651477 |
Homozygosity mapping reveals null mutations in FAM161A as a cause of autosomal-recessive retinitis pigmentosa. | Bandah-Rozenfeld D | American journal of human genetics | 2010 | PMID: 20705279 |
Nonsense mutations in FAM161A cause RP28-associated recessive retinitis pigmentosa. | Langmann T | American journal of human genetics | 2010 | PMID: 20705278 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=FAM161A | - | - | - | - |
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Text-mined citations for rs200691042 ...
HelpRecord last updated Oct 08, 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.