ClinVar Miner

Submissions for variant NM_017433.5(MYO3A):c.4505T>G (p.Leu1502Ter)

gnomAD frequency: 0.00003  dbSNP: rs754217606
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000778281 SCV000914457 uncertain significance Autosomal recessive nonsyndromic hearing loss 30 2018-12-11 criteria provided, single submitter clinical testing The MYO3Ac.4505T>G (p.Leu1502Ter) variant is a stop-gained variant predicted to result in premature termination of the protein. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. The p.Leu1502Ter variant is reported at a frequency of 0.000508 in the Ashkenazi Jewish population from the Genome Aggregation Database. Based on the variant frequency, disease prevalence, disease penetrance, and inheritance mode, this variant could not be ruled out of causing disease. Based on the potential impact of stop-gained variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for nonsyndromic hearing loss, recessive. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
GeneDx RCV001552156 SCV001772801 uncertain significance not provided 2021-05-11 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001552156 SCV002233580 pathogenic not provided 2022-10-17 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 631634). This variant has not been reported in the literature in individuals affected with MYO3A-related conditions. This variant is present in population databases (rs754217606, gnomAD 0.05%). This sequence change creates a premature translational stop signal (p.Leu1502*) in the MYO3A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYO3A are known to be pathogenic (PMID: 12032315, 23990876).

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