Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular 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, |
RCV000764890 | SCV000896050 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 30 | 2021-09-07 | criteria provided, single submitter | clinical testing | |
Gene |
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. |