Submissions for variant NM_001252024.2(TRPM1):c.3064C>T (p.Arg1022Ter)

gnomAD frequency: 0.00004  dbSNP: rs369742878

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000790811	SCV000227921	pathogenic	not provided	2014-02-18	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000790811	SCV002246051	pathogenic	not provided	2024-03-30	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg1000*) in the TRPM1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TRPM1 are known to be pathogenic (PMID: 19896113, 19966281, 20300565). This variant is present in population databases (rs369742878, gnomAD 0.009%). This premature translational stop signal has been observed in individual(s) with TRPM1-related conditions (PMID: 25999674). ClinVar contains an entry for this variant (Variation ID: 167748). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV000790811	SCV004014271	likely pathogenic	not provided	2022-12-27	criteria provided, single submitter	clinical testing	Observed with a second TRPM1 variant in a patient with suspected retinitis pigmentosa based on clinical history, although patient specific clinical information was not provided (van Huet et al., 2015); Observed in the heterozygous state in an individual with schizophrenia, but additional clinical information and familial segregation data were not provided (Hu et al., 2014); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 24126932, 25999674)
PreventionGenetics, part of Exact Sciences	RCV003422046	SCV004118373	pathogenic	TRPM1-related disorder	2023-08-08	criteria provided, single submitter	clinical testing	The TRPM1 c.3115C>T variant is predicted to result in premature protein termination (p.Arg1039*). This variant has been reported in the compound heterozygous state in an individual with retinitis pigmentosa (referred to as c.2998C>T (p.Arg1000*) in van Huet et al. 2015. PubMed ID: 25999674). This variant is reported in 0.010% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/15-31323249-G-A). Nonsense variants in TRPM1 are expected to be pathogenic. This variant is interpreted as pathogenic.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000790811	SCV001800671	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000790811	SCV001953710	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000790811	SCV001967413	pathogenic	not provided		no assertion criteria provided	clinical testing