Submissions for variant NM_001018005.2(TPM1):c.522C>T (p.Ser174=)

gnomAD frequency: 0.00010  dbSNP: rs200173919

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036339	SCV000059991	likely benign	not specified	2007-08-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000312289	SCV000393211	uncertain significance	Dilated cardiomyopathy 1Y	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.
Illumina Laboratory Services, Illumina	RCV001094326	SCV000393212	uncertain significance	Hypertrophic cardiomyopathy 3	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.
Invitae	RCV000350673	SCV000558816	likely benign	Hypertrophic cardiomyopathy	2023-11-15	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000777777	SCV000913748	likely benign	Cardiomyopathy	2018-07-09	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000777777	SCV001333155	benign	Cardiomyopathy	2018-08-03	criteria provided, single submitter	clinical testing
GeneDx	RCV001705660	SCV001827307	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002336122	SCV002645318	likely benign	Cardiovascular phenotype	2019-11-21	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
CeGaT Center for Human Genetics Tuebingen	RCV001705660	SCV003917398	likely benign	not provided	2023-02-01	criteria provided, single submitter	clinical testing	TPM1: BP4, BP7