ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.4916C>T (p.Thr1639Met) (rs200848641)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000482590 SCV000571184 uncertain significance not provided 2017-03-09 criteria provided, single submitter clinical testing The T1639M variant in the MYO7A gene has been reported previously, along with a second MYO7A missense variant, in an individual with severe-profound non-syndromic hearing loss (Sloan-Heggen et al., 2016). The T1639M variant is observed in 34/9,748 (0.349%) alleles from individuals of African background in the ExAC dataset; no individuals were homozygous (Lek et al., 2016). The T1639M 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. This substitution occurs at a position that is conserved in mammals, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret T1639M as a variant of uncertain significance.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000825982 SCV000967470 uncertain significance not specified 2018-08-08 criteria provided, single submitter clinical testing The p.Thr1639Met variant in MYO7A has been reported in 1 individual who harbored a second variant of uncertain significance in MYO7A (Sloan-Heggen 2016). This v ariant has been identified in 0.23% (54/24014) of African chromosomes by the Gen ome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org/) and is repo rted in ClinVar (Variation ID: 421863). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogeni c role. Computational prediction tools and conservation analysis suggest that th e p.Thr1630Met variant may impact the protein, though this information is not pr edictive enough to determine pathogenicity. In summary, the clinical significanc e of the p.Thr1639Met variant is uncertain. ACMG/AMP Criteria applied: PP3, BS1_ Supporting.

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