ClinVar Miner

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

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
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, 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.