ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.6025del (p.Ala2009fs)

dbSNP: rs397516326
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000844724 SCV000059870 pathogenic Rare genetic deafness 2016-03-17 criteria provided, single submitter clinical testing The p.Ala2009fs variant in MYO7A has been reported in at least 10 unrelated indi viduals with Usher syndrome including 4 homozygotes and 3 compound heterozygotes , segregated with disease in one family, and was absent from over 400 race-match ed control chromosomes or large population studies (Bharadwaj 2000, Gerber 2006, Jaijo 2007, Jaijo 2009, Maubaret 2005, Najera 2002, Roux 2006, LMM data). This variant is predicted to cause a frameshift, which alters the protein's amino aci d sequence beginning at codon 2009 and leads to a premature stop codon 32 codons downstream. This alteration is then predicted to lead to a truncated or absent protein. In summary, this variant meets our criteria to be classified as pathoge nic for Usher syndrome in an autosomal recessive manner. ACMG/AMP Criteria appli ed: PVS1, PM2, PM3_Very Strong, PP4.
Labcorp Genetics (formerly Invitae), Labcorp RCV001046525 SCV001210430 pathogenic not provided 2024-01-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ala2009Profs*32) in the MYO7A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYO7A are known to be pathogenic (PMID: 8900236, 25404053). This variant is present in population databases (rs752136791, gnomAD 0.003%). This premature translational stop signal has been observed in individuals with Usher syndrome (PMID: 10930322, 25404053). This variant is also known as Met2018 (1-bp del G). ClinVar contains an entry for this variant (Variation ID: 43313). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001075853 SCV001241492 pathogenic Retinal dystrophy 2019-08-08 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002477080 SCV002779230 pathogenic Autosomal dominant nonsyndromic hearing loss 11; Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1 2021-11-09 criteria provided, single submitter clinical testing
Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals RCV000036218 SCV000259090 pathogenic Usher syndrome type 1 2015-01-30 no assertion criteria provided clinical testing
Counsyl RCV000036218 SCV001132253 pathogenic Usher syndrome type 1 2017-07-07 no assertion criteria provided clinical testing
Counsyl RCV000984197 SCV001132254 pathogenic Autosomal recessive nonsyndromic hearing loss 2 2017-07-07 no assertion criteria provided clinical testing
Natera, Inc. RCV001275528 SCV001460743 pathogenic Usher syndrome type 1B 2020-09-16 no assertion criteria provided clinical testing

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