ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.1232T>C (p.Val411Ala)

gnomAD frequency: 0.00004  dbSNP: rs369916141
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Total submissions: 4
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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 RCV000036043 SCV000059695 uncertain significance not specified 2017-06-23 criteria provided, single submitter clinical testing The p.Val411Ala variant in MYO7A has been reported in 1 individual with autosoma l recessive hearing loss and 1 individual with unilateral hearing loss, however a second variant in MYO7A was not detected in either individual (Kothiyal 2010, LMM unpublished data, ClinVar Variation ID 43139). In addition, the variant was reported in 1 individual with autosomal dominant retinitis pigmentosa, however t his individual carried another variant that was more likely responsible for the disease (Sujirakul 2015). This variant has also been identified in 4/34106 Latin o chromosomes and 3/23546 African chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs369916141); however this fre quency is not high enough to rule out a pathogenic role. Computational predictio n tools and conservation analysis suggest that the variant may impact the protei n, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Val411Ala variant is uncertain.
Counsyl RCV000665699 SCV000789862 uncertain significance Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1 2017-02-23 criteria provided, single submitter clinical testing
Invitae RCV001313198 SCV001503682 uncertain significance not provided 2024-01-18 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 411 of the MYO7A protein (p.Val411Ala). This variant is present in population databases (rs369916141, gnomAD 0.01%). This missense change has been observed in individual(s) with deafness and/or retinitis pigmentosa (PMID: 26164827, 33297549). ClinVar contains an entry for this variant (Variation ID: 43139). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYO7A protein function with a positive predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Natera, Inc. RCV001275900 SCV001461551 uncertain significance Usher syndrome type 1B 2020-09-16 no assertion criteria provided clinical testing

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