ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.1556G>A (p.Gly519Asp) (rs111033206)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000844714 SCV000059707 pathogenic Rare genetic deafness 2016-06-23 criteria provided, single submitter clinical testing The p.Gly519Asp variant in MYO7A has now been identified in the homozygous or co mpound heterozygous state in at least 6 individuals with clinical features of Us her syndrome type I (Bharadwaj 2000, Roux 2006, Bonnet 2011, LMM data). It has b een identified in 2/66462 European chromosomes by the Exome Aggregation Consorti um (ExAC,; dbSNP rs111033206). Although this vari ant has been identified in the general population, its frequency is low enough t o be consistent with the carrier frequency. In summary, this variant meets crite ria to be classified as pathogenic for autosomal recessive Usher syndrome.
Counsyl RCV000669343 SCV000794089 likely pathogenic Deafness, autosomal recessive 2; Usher syndrome type 1 2017-09-08 criteria provided, single submitter clinical testing
Invitae RCV000817879 SCV000958464 likely pathogenic not provided 2020-01-02 criteria provided, single submitter clinical testing This sequence change replaces glycine with aspartic acid at codon 519 of the MYO7A protein (p.Gly519Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is present in population databases (rs111033206, ExAC 0.003%). This variant has been observed in several individuals with Usher syndrome (PMID: 21569298, 10930322, 16679490, 21873662, 25468891). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 43151). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
GeneReviews RCV000036055 SCV000268740 pathogenic Usher syndrome type 1 2016-05-19 no assertion criteria provided literature only

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