Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Revvity Omics, |
RCV001783827 | SCV002023686 | likely pathogenic | Autosomal recessive nonsyndromic hearing loss 16 | 2020-07-10 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV004017868 | SCV004848671 | pathogenic | Rare genetic deafness | 2022-06-23 | criteria provided, single submitter | clinical testing | The p.Glu1504ArgfsX32 variant in STRC has been reported in two individuals with nonsyndromic hearing loss, one of whom was homozygous for the variant and the other was compound heterozygous with a large deletion (Mahfood 2019 PMID: 30758234, Sommen 2016 PMID: 27068579). It has also been identified in 0.001% (1/67988) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org).However, this frequency is low enough to be consistent with a recessive allele frequency. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 1504 and leads to a premature termination codon 32 amino acids downstream. Loss of function of the STRC gene is an established disease mechanism in autosomal recessive nonsyndromic hearing loss. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive nonsyndromic hearing loss. ACMG/AMP Criteria applied: PVS1, PM3, PM2_Supporting. |