ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.3502C>T (p.Arg1168Trp)

gnomAD frequency: 0.00002  dbSNP: rs554073390
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668846 SCV000793518 uncertain significance Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1 2017-08-23 criteria provided, single submitter clinical testing
Baylor-Hopkins Center for Mendelian Genomics, Johns Hopkins University School of Medicine RCV000790513 SCV000929843 uncertain significance Autosomal dominant nonsyndromic hearing loss 11 criteria provided, single submitter research
Invitae RCV001242948 SCV001416074 pathogenic not provided 2024-01-24 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1168 of the MYO7A protein (p.Arg1168Trp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with clinical features of Usher syndrome and autosomal recessive deafness (PMID: 20052763, 21436283, 30303587, 33187236; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 553405). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic.
Preventiongenetics, part of Exact Sciences RCV003420184 SCV004108459 uncertain significance MYO7A-related condition 2023-08-28 criteria provided, single submitter clinical testing The MYO7A c.3502C>T variant is predicted to result in the amino acid substitution p.Arg1168Trp. This variant was reported in the heterozygous state without a second potentially causative variant in an individual with Usher syndrome (Le Guédard-Méreuze et al. 2010. PubMed ID: 20052763), and in the homozygous state in two siblings from a consanguineous family with nonsyndromic hearing loss (Doll et al. 2020. PubMed ID: 33187236). This variant occurs at the penultimate nucleotide of exon 27, although in vitro studies found no effect on splicing (Le Guédard-Méreuze et al. 2010. PubMed ID: 20052763). This variant is reported in 0.0085% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-76895759-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
CeGaT Center for Human Genetics Tuebingen RCV001242948 SCV004131121 uncertain significance not provided 2023-01-01 criteria provided, single submitter clinical testing MYO7A: PP3
University of Washington Center for Mendelian Genomics, University of Washington RCV001291475 SCV001479979 likely pathogenic Hearing loss, autosomal recessive no assertion criteria provided research

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