ClinVar Miner

Submissions for variant NM_016239.4(MYO15A):c.10263C>G (p.Ile3421Met)

gnomAD frequency: 0.00001  dbSNP: rs748246442
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 RCV001756661 SCV001986244 uncertain significance not provided 2023-12-14 criteria provided, single submitter clinical testing Identified in an additional patient with autosomal recessive sensorineural hearing loss in published literature (PMID: 23967202); In silico analysis supports that this missense variant does not alter protein structure/function; In silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 27375115, 30579064, 30953472, 29482514, 34455394, 23967202)
Labcorp Genetics (formerly Invitae), Labcorp RCV001756661 SCV004276684 pathogenic not provided 2024-01-29 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 3421 of the MYO15A protein (p.Ile3421Met). This variant is present in population databases (rs748246442, gnomAD 0.05%). This missense change has been observed in individual(s) with deafness (PMID: 23967202, 25792667, 29482514). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1303162). 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 not expected to disrupt MYO15A protein function with a negative predictive value of 95%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

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.