ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.640G>A (p.Gly214Arg) (rs111033283)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000667735 SCV000792234 pathogenic Deafness, autosomal recessive 2; Usher syndrome, type 1 2017-06-13 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724325 SCV000232036 pathogenic not provided 2014-10-21 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000515404 SCV000611217 pathogenic Deafness, autosomal dominant 11; Deafness, autosomal recessive 2; Usher syndrome, type 1 2017-05-18 criteria provided, single submitter clinical testing
Invitae RCV000724325 SCV000962274 likely pathogenic not provided 2018-10-16 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 214 of the MYO7A protein (p.Gly214Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed as homozygous or in combination with other MYO7A variants in several individuals affected with Usher syndrome (PMID: 16470552, 24199935, 9382091, 26969326). ClinVar contains an entry for this variant (Variation ID: 43327). 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.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000036233 SCV000059885 pathogenic Rare genetic deafness 2016-08-23 criteria provided, single submitter clinical testing The p.Gly214Arg variant in MYO7A has been reported in over 10 probands with Ushe r syndrome who were either homozygous for the variant or compound heterozygous w ith a second pathogenic or likely pathogenic variant in MYO7A (Adato 1997, Apari si 2013, Bujakowska 2014, Jaijo 2011, Jaijo 2009, Jaijo 2006, Le Quesne Stabej 2 012, Riazuddin 2008, Roux 2011, LMM data). It has not been identified in large p opulation studies. Computational prediction tools and conservation analyses sugg est that this variant may impact the protein. In summary, this variant meets our criteria to be classified as pathogenic for Usher syndrome in an autosomal rece ssive manner based on its presence in homozygosity or compound heterozygosity wi th a second pathogenic allele in many individuals with Usher syndrome, and low f requency in the general population.

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