ClinVar Miner

Submissions for variant NM_001042702.5(PJVK):c.499C>T (p.Arg167Ter)

gnomAD frequency: 0.00010  dbSNP: rs118203989
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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 RCV000223480 SCV000271351 pathogenic Rare genetic deafness 2020-06-01 criteria provided, single submitter clinical testing The p.Arg167X variant in DFNB59 has been reported in 2 individuals with hearing loss (1 Turkish and 1 Iranian), and segregated with disease in at least 1 affected family member (Collin 2007, Akhtarkhavari 2014). All affected individuals were homozygous. This variant has been identified in 0.01% (18/128640) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. This nonsense variant leads to a premature termination codon at position 167, which is predicted to lead to a truncated or absent protein. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive hearing loss. ACMG/AMP Criteria applied: PVS1, PM2_Supporting, PM3, PP1_Supporting.
GeneDx RCV003325448 SCV004031688 likely pathogenic not provided 2024-09-11 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; This variant is associated with the following publications: (PMID: 25525159, 22530481, 27018795, 35052489, 21696384, 28964305, 28483220, 26226137, 23804846, 17373699)
Labcorp Genetics (formerly Invitae), Labcorp RCV003325448 SCV004292654 pathogenic not provided 2024-01-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg167*) in the DFNB59 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DFNB59 are known to be pathogenic (PMID: 17301963, 17718875). This variant is present in population databases (rs118203989, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with autosomal recessive deafness (PMID: 17373699). ClinVar contains an entry for this variant (Variation ID: 1300). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000001363 SCV000021513 pathogenic Autosomal recessive nonsyndromic hearing loss 59 2007-07-01 no assertion criteria provided literature only

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