ClinVar Miner

Submissions for variant NM_001252024.2(TRPM1):c.281A>G (p.Tyr94Cys)

gnomAD frequency: 0.00019  dbSNP: rs200514769
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001069997 SCV001235203 pathogenic not provided 2024-01-14 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 72 of the TRPM1 protein (p.Tyr72Cys). This variant is present in population databases (rs200514769, gnomAD 0.04%). This missense change has been observed in individual(s) with congenital stationary night blindness (CSNB) (PMID: 19896113, 28559085, 29522070). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 863108). 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 TRPM1 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV001069997 SCV001246416 pathogenic not provided 2020-06-01 criteria provided, single submitter clinical testing
GeneDx RCV001069997 SCV002568554 uncertain significance not provided 2022-08-12 criteria provided, single submitter clinical testing Observed multiple times with an additional TRPM1 variant in published literature, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes (Audo et al., 2009; Stone et al., 2017; Zhu et al., 2022); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34426522, 28559085, 29522070, 35456422, 19896113)

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