Submissions for variant NM_001276345.2(TNNT2):c.52+7G>A

gnomAD frequency: 0.00007  dbSNP: rs374443596

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036599	SCV000060254	likely benign	not specified	2015-01-05	criteria provided, single submitter	clinical testing	c.52+7G>A in intron 3 of TNNT2: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. This variant has been identified in 0.1% (12 /8766) of East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http ://exac.broadinstitute.org; dbSNP rs374443596).
Invitae	RCV001086777	SCV000262007	benign	Hypertrophic cardiomyopathy 2; Dilated cardiomyopathy 1D; Cardiomyopathy, familial restrictive, 3	2024-01-17	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000381877	SCV000353372	uncertain significance	Left ventricular noncompaction cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000287633	SCV000353373	uncertain significance	Dilated Cardiomyopathy, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000342545	SCV000353374	uncertain significance	Cardiomyopathy, familial restrictive, 3	2018-01-12	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	RCV000406678	SCV000353375	uncertain significance	Hypertrophic cardiomyopathy 2	2018-01-12	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	RCV000036599	SCV000514923	benign	not specified	2015-06-29	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587892	SCV000697565	benign	not provided	2016-02-15	criteria provided, single submitter	clinical testing	Variant summary: c.52+7G>A affects a non-conserved nucleotide, resulting in an intronic change. Mutation taster predicts benign outcome. 4/5 programs in Alamut predict that this variant does not affect normal splicing. This variant was found in 22/121412 control chromosomes at a frequency of 0.0001812, predominantly observed in East Asian subpopulation with MAF of 0.001387. This frequency exceeds the maximal expected frequency of a pathogenic allele (0.00005), suggesting this variant is benign ethnic-specific polymorphism. This variant was reported in one DCM patient and was classified by authors as likely benign (Pugh_2014). In addition, multiple clinical laboratories (via ClinVar) classified this variant as benign/likely benign and one lab classified this variant as VUS. Taken together, this variant was classified as Benign.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769741	SCV000901163	likely benign	Cardiomyopathy	2023-02-10	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000036599	SCV001918396	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000587892	SCV001959127	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000587892	SCV001971367	likely benign	not provided		no assertion criteria provided	clinical testing