ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.1927G>A (p.Val643Met) (rs61749417)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000174470 SCV000225778 benign not specified 2015-05-13 criteria provided, single submitter clinical testing
GeneDx RCV000174470 SCV000321341 uncertain significance not specified 2017-08-10 criteria provided, single submitter clinical testing The V643M variant of uncertain significance has been reported previously in the literature several times in association with Stargardt disease (Briggs et al., 2001; Alapati et al., 2014; Wang et al., 2014). However, in many of these cases the variant was seen in conjunction with other explanatory pathogenic variants. The NHLBI Exome Sequencing Project reports V643M was observed in 80/4,406 (1.8%) alleles from individuals of African American background, indicating it may be a rare variant in this population. Additionally, the 1000 Genomes Project Consortium reports that V643M was also observed in 35/1322 (2.7%) alleles from individuals of African ancestry. The variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species; however, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Illumina Clinical Services Laboratory,Illumina RCV000353201 SCV000359460 likely benign Stargardt Disease, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000260757 SCV000359461 likely benign Macular degeneration 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000318324 SCV000359462 likely benign Cone-Rod Dystrophy, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000356519 SCV000359463 likely benign Retinitis Pigmentosa, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000085445 SCV001038385 benign not provided 2019-12-31 criteria provided, single submitter clinical testing
Mendelics RCV000986369 SCV001135357 benign Stargardt disease 1 2019-05-28 criteria provided, single submitter clinical testing
Blueprint Genetics RCV001075850 SCV001241489 uncertain significance Retinal dystrophy 2019-08-02 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001098279 SCV001254633 likely benign ABCA4-Related Disorders 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Retina International RCV000085445 SCV000117582 not provided not provided no assertion provided not provided

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