ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.494C>T (p.Thr165Met)

gnomAD frequency: 0.00001  dbSNP: rs111033174
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Total submissions: 9
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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 RCV000036169 SCV000059821 pathogenic Rare genetic deafness 2012-11-29 criteria provided, single submitter clinical testing The Thr165Met variant in MYO7A has been reported in 4 individuals with Usher syn drome and was absent from 1116 chromosomes (Roux 2011, Gerber 2006, Ouyang 2005, Roux 2006). Three of these individuals were homozygous or compound heterozygous . In addition, this variant was identified in one individual with Usher syndrome by our laboratory who also carried a second pathogenic variant in MYO7A. In su mmary, this variant meets our criteria to be classified as pathogenic (http://pc pgm.partners.org/LMM).
GeneDx RCV000434773 SCV000521010 pathogenic not provided 2020-11-03 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 16400615, 15660226, 16963483, 24831256, 25404053, 27460420, 21436283, 31479088, 30800556, 24014347, 26969326, 16679490, 33576163, 31589614)
Labcorp Genetics (formerly Invitae), Labcorp RCV000434773 SCV001375127 pathogenic not provided 2025-01-01 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 165 of the MYO7A protein (p.Thr165Met). This variant is present in population databases (rs111033174, gnomAD 0.006%). This missense change has been observed in individual(s) with Usher syndrome (PMID: 16400615, 16679490, 24831256, 25404053, 26969326, 27460420). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 43264). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt MYO7A protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000434773 SCV001447304 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg RCV004814946 SCV005072145 likely pathogenic Retinal dystrophy 2012-01-01 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005003426 SCV005632191 pathogenic Autosomal dominant nonsyndromic hearing loss 11; Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1 2024-05-31 criteria provided, single submitter clinical testing
Counsyl RCV000666360 SCV000790639 likely pathogenic Autosomal recessive nonsyndromic hearing loss 2 2017-04-04 no assertion criteria provided clinical testing
Natera, Inc. RCV001826551 SCV002093120 pathogenic Usher syndrome type 1B 2020-10-27 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004734546 SCV005359654 pathogenic MYO7A-related disorder 2024-07-12 no assertion criteria provided clinical testing The MYO7A c.494C>T variant is predicted to result in the amino acid substitution p.Thr165Met. This variant has been reported as pathogenic for autosomal recessive Usher syndrome (Ouyang et al. 2005. PubMed ID: 15660226; Aparisi et al. 2014. PubMed ID: 25404053; Table S3, Sloan-Heggen et al 2016. PubMed ID: 26969326; Gerber et al. 2006. PubMed ID: 16400615; Table S1, Bonnet et al. 2016. PubMed ID: 27460420; Roux et al. 2006. PubMed ID: 16679490; Rong et al. 2014. PubMed ID: 24831256; Supplementary Table 1, Weisschuh. 2024. PubMed ID: 37734845 ). This variant is reported in 0.0062% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant is interpreted as pathogenic.

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