ClinVar Miner

Submissions for variant NM_017433.5(MYO3A):c.4840C>T (p.Gln1614Ter)

gnomAD frequency: 0.00022  dbSNP: rs146106052
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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 RCV000220046 SCV000272132 uncertain significance not specified 2015-06-23 criteria provided, single submitter clinical testing The p.Gln1614X variant in MYO3A has not been previously reported in individuals with hearing loss, but has been identified in 0.04% (23/62360) European chromoso mes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; d bSNP rs146106052). Although this variant has been seen in the general population , its frequency is not high enough to rule out a pathogenic role. This nonsense variant leads to a premature termination codon at position 1614, located 3 codon s upstream of the nascent termination codon. Thus, the variant is predicted to l ead to a slightly truncated protein, missing the last 3 amino acids of the norma l protein. However, it is not clear whether this truncation will have a deleteri ous impact on the protein's structure or function. In summary, the clinical sign ificance of the p.Gln1614X variant is uncertain.
Fulgent Genetics, Fulgent Genetics RCV000764890 SCV000896050 uncertain significance Autosomal recessive nonsyndromic hearing loss 30 2021-09-07 criteria provided, single submitter clinical testing
GeneDx RCV001562089 SCV001784803 uncertain significance not provided 2021-08-12 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation, although loss-of-function variants have not been reported downstream of this position in the protein; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV001562089 SCV002155851 uncertain significance not provided 2023-12-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1614*) in the MYO3A gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 3 amino acid(s) of the MYO3A protein. This variant is present in population databases (rs146106052, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with MYO3A-related conditions. ClinVar contains an entry for this variant (Variation ID: 228985). 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.

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