Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular 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unilateral hearing loss, however a second variant in MYO7A was not detected in either individual (Kothiyal 2010, LMM unpublished data, ClinVar Variation ID 43139).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, |
RCV001275900 | SCV001461551 | uncertain significance | Usher syndrome type 1B | 2020-09-16 | no assertion criteria provided | clinical testing |