Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000154022 | SCV000203650 | uncertain significance | not provided | 2017-09-21 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000154022 | SCV001250112 | pathogenic | not provided | 2020-06-01 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000154022 | SCV001517586 | pathogenic | not provided | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 928 of the TRPM1 protein (p.Arg928Trp). This variant is present in population databases (rs727504182, gnomAD 0.008%). This missense change has been observed in individuals with congenital stationary night blindness (CSNB) (PMID: 28341476, 31725702, 32141364, 35119454). ClinVar contains an entry for this variant (Variation ID: 167749). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TRPM1 protein function. This variant disrupts the p.Arg928 amino acid residue in TRPM1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 24715752, 31427709). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |