Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000607453 | SCV000712563 | likely pathogenic | Rare genetic deafness | 2023-02-02 | criteria provided, single submitter | clinical testing | The p.Thr1709Ala variant in STRC has been reported in 4 individuals with hearing loss, all of whom carried a second pathogenic STRC variant (Vona 2015, Kim 2016, Baux 2017, LMM data). It has also been identified in 0.06% (12/19778) of East Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis suggest that the variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive nonsyndromic hearing loss. ACMG/AMP Criteria applied: PM3_Strong, PM2_Supporting, PP3. (This variant did not meet the variant calling quality criteria, and was included because it has been previously reported as a clinically significant variant.) |
| Mayo Clinic Laboratories, |
RCV003480710 | SCV004225748 | likely pathogenic | not provided | 2022-02-21 | criteria provided, single submitter | clinical testing | PM2_supporting, PM3 |
| Prevention |
RCV003403414 | SCV004120084 | uncertain significance | STRC-related disorder | 2024-06-18 | no assertion criteria provided | clinical testing | The STRC c.5125A>G variant is predicted to result in the amino acid substitution p.Thr1709Ala. This variant has been reported along with another potentially pathogenic variant in three patients with hearing loss. Although two of these studies confirmed the location of this variant in the STRC functional gene, further evidence of pathogenicity was not presented (Vona et al. 2015. PubMed ID: 26011646; Kim et al. 2016. PubMed ID: 27057829; Kim et al. 2020. PubMed ID: 32203226; Baux et al. 2017. PubMed ID: 29196752). This variant in exon 28 corresponds to a known STRCP1 pseudogene variant, and therefore presence of this variant in the functional gene (as in this patient) may be indicative of a large deletion or gene conversion event on the same allele. While we suspect this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |