Submissions for variant NM_001018005.2(TPM1):c.840T>C (p.Asp280=)

gnomAD frequency: 0.00001  dbSNP: rs749271066

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001119718	SCV001278149	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.
Illumina Laboratory Services, Illumina	RCV001119719	SCV001278150	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.
Color Diagnostics, LLC DBA Color Health	RCV001192109	SCV001360085	likely benign	Cardiomyopathy	2018-12-31	criteria provided, single submitter	clinical testing
Invitae	RCV001495214	SCV001699885	likely benign	Hypertrophic cardiomyopathy	2024-01-15	criteria provided, single submitter	clinical testing
GeneDx	RCV001593282	SCV001814387	likely benign	not provided	2021-05-13	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002445390	SCV002679380	uncertain significance	Cardiovascular phenotype	2024-05-06	criteria provided, single submitter	clinical testing	The c.840T>C variant (also known as p.D280D), located in coding exon 9 of the TPM1 gene, results from a T to C substitution at nucleotide position 840. This nucleotide substitution does not change the aspartic acid at codon 280. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV003963064	SCV004790166	likely benign	TPM1-related disorder	2019-03-26	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
All of Us Research Program, National Institutes of Health	RCV001495214	SCV004815471	likely benign	Hypertrophic cardiomyopathy	2024-02-05	criteria provided, single submitter	clinical testing