ClinVar Miner

Submissions for variant NM_017636.4(TRPM4):c.1744G>A (p.Gly582Ser)

gnomAD frequency: 0.00043  dbSNP: rs172149856
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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000208117 SCV000264272 uncertain significance Brugada syndrome 2015-05-21 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000029158 SCV000290321 likely benign Progressive familial heart block type IB 2025-01-31 criteria provided, single submitter clinical testing
GeneDx RCV001090742 SCV000521220 likely benign not provided 2020-03-31 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 21887725, 22750058, 26350513, 23382873, 27884173, 27207958, 28341588, 26820365)
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000029158 SCV000745391 uncertain significance Progressive familial heart block type IB 2017-11-07 criteria provided, single submitter clinical testing
Mendelics RCV000990241 SCV001141119 uncertain significance Progressive familial heart block, type 1A 2019-05-28 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000029158 SCV001295714 uncertain significance Progressive familial heart block type IB 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Ambry Genetics RCV002399335 SCV002711587 benign Cardiovascular phenotype 2018-12-03 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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 RCV001090742 SCV003799326 uncertain significance not provided 2022-03-17 criteria provided, single submitter clinical testing The p.Gly582Ser variant (rs172149856) has been previously reported in a cardiac conductive block patient who also carried the p.Ala432Thr variant but this variant has not been reported alone (Stallmeyer et al 2012). This variant is listed in the NHLBI GO Exome Sequencing Project with an overall population frequency of 0.07 percent and is listed in the Exome Aggregation Consortium Browser with an overall population frequency of 0.05 percent. The glycine at position 582 is moderately conserved (considering 15 species, Alamut v2.7.1) and computational analyses of the effects of the p.Gly582Ser variant on protein structure and function predict this variant to be benign (SIFT: tolerated, MutationTaster: polymorphism, PolyPhen-2: benign). Because the p.Gly582Ser variant has not been observed without the p.Ala432Thr variant there is not enough evidence to classify this variant with certainty. Pathogenic variants of TRPM4 are inherited in an autosomal dominant manner and are associated with progressive familial heart block, type IB (MIM: 604599).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004700278 SCV005203361 likely benign not specified 2024-07-21 criteria provided, single submitter clinical testing
OMIM RCV000029158 SCV000051803 pathogenic Progressive familial heart block type IB 2012-01-01 no assertion criteria provided literature only
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV001090742 SCV001800097 uncertain significance not provided no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV001090742 SCV001920025 uncertain significance not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001090742 SCV001958157 uncertain significance not provided no assertion criteria provided clinical testing

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