Submissions for variant NM_017636.4(TRPM4):c.1368C>G (p.Thr456=)

gnomAD frequency: 0.00274  dbSNP: rs56118173

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000999846	SCV000290316	benign	Progressive familial heart block type IB	2024-01-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000999846	SCV000414293	uncertain significance	Progressive familial heart block type IB	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV001722262	SCV000532175	likely benign	not provided	2021-04-28	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000620174	SCV000735092	likely benign	Cardiovascular phenotype	2015-07-17	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001722262	SCV000884736	benign	not provided	2023-10-26	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000420786	SCV001918214	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000420786	SCV001960112	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001722262	SCV001974357	likely benign	not provided		no assertion criteria provided	clinical testing