ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.6487G>A (p.Gly2163Ser) (rs747656448)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000669855 SCV000794647 likely pathogenic Deafness, autosomal recessive 2; Usher syndrome, type 1 2017-10-12 criteria provided, single submitter clinical testing
GeneDx RCV000520963 SCV000617515 pathogenic not provided 2018-11-07 criteria provided, single submitter clinical testing The G2163S variant in the MYO7A gene has been reported previously in the heterozygous state with a second MYO7A variant in an individual with Usher syndrome type I, and in the homozygous state in multiple families with nonsyndromic autosomal recessive hearing loss (Janecke et al., 1999; Shahin et al., 2010; Diaz-Horta et al., 2012; Asgharzade et al., 2017). The G2163S variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The G2163S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Functional studies indicate that the G2163S variant disrupts MYO7A binding to adaptor protein harmonin, which impacts mechanotransduction of cadherin linkages between stererocilia and microvilli (Yu et al., 2017). We interpret G2163S as a pathogenic variant.
Hereditary Research Laboratory,Bethlehem University RCV000454276 SCV000538106 pathogenic Deafness, autosomal recessive 2 2016-06-04 no assertion criteria provided research severe-profound
Invitae RCV000520963 SCV000954261 pathogenic not provided 2018-12-10 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 2163 of the MYO7A protein (p.Gly2163Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs747656448, ExAC 0.006%). This variant has been observed to segregate with MYO7A-related conditions in several families and has been observed in additional affected individuals (10094549, 19375528, 23770805, 26226137, 28451532, 19888295). ClinVar contains an entry for this variant (Variation ID: 402267). For these reasons, this variant has been classified as Pathogenic.

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