Submissions for variant NM_017636.4(TRPM4):c.337C>T (p.Arg113Cys)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Clinical Center for Gene Diagnosis and Therapy, Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University	RCV003319258	SCV003932384	uncertain significance	Primary dilated cardiomyopathy	2023-06-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV005102472	SCV005811917	uncertain significance	Progressive familial heart block type IB	2024-10-08	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 113 of the TRPM4 protein (p.Arg113Cys). This variant is present in population databases (rs760925558, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with TRPM4-related conditions. ClinVar contains an entry for this variant (Variation ID: 2505325). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV005240734	SCV005887107	uncertain significance	not specified	2025-01-31	criteria provided, single submitter	clinical testing	Variant summary: TRPM4 c.337C>T (p.Arg113Cys) results in a non-conservative amino acid change located in the SLOG in TRPM domain (IPR041491) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251182 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.337C>T in individuals affected with TRPM4-related conditions and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 2505325). Based on the evidence outlined above, the variant was classified as uncertain significance.