Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000085329 | SCV003494884 | likely pathogenic | not provided | 2023-06-05 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Thr185 amino acid residue in RS1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10234514, 17525175, 28348004). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RS1 protein function. ClinVar contains an entry for this variant (Variation ID: 98988). This variant has not been reported in the literature in individuals affected with RS1-related conditions. This variant is present in population databases (rs61753173, gnomAD 0.005%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 185 of the RS1 protein (p.Thr185Met). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003488382 | SCV004241868 | uncertain significance | not specified | 2023-12-06 | criteria provided, single submitter | clinical testing | Variant summary: RS1 c.554C>T (p.Thr185Met) results in a non-conservative amino acid change located in the Coagulation factor 5/8 C-terminal domain (IPR000421) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 5.5e-06 in 182758 control chromosomes (gnomAD). c.554C>T has been reported in the literature in individuals affected with X-linked juvenile retinoschisis (examples: Mano_2022, Gao_2021). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 33124204, 34991515, 34645606). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| Retina International | RCV000085329 | SCV000117466 | not provided | not provided | no assertion provided | not provided |