ClinVar Miner

Submissions for variant NM_001276345.2(TNNT2):c.63T>G (p.Val21=) (rs397516477)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000036608 SCV000060263 likely benign not specified 2010-07-22 criteria provided, single submitter clinical testing p.Val21Val in exon 4 of TNNT2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence.
Invitae RCV000552155 SCV000646905 likely benign Familial hypertrophic cardiomyopathy 2; Left ventricular noncompaction 6; Familial restrictive cardiomyopathy 3 2019-10-04 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769740 SCV000901162 benign Cardiomyopathy 2017-10-17 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000036608 SCV000918320 benign not specified 2018-10-29 criteria provided, single submitter clinical testing Variant summary: TNNT2 c.63T>G alters a non-conserved nucleotide resulting in a synonymous change. The variant allele was found at a frequency of 8.4e-05 in 273784 control chromosomes, predominantly at a frequency of 0.0011 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 6.29 fold of the estimated maximal expected allele frequency for a pathogenic variant in TNNT2 causing Cardiomyopathy phenotype (0.00018), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. To our knowledge, no occurrence of c.63T>G in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Illumina Clinical Services Laboratory,Illumina RCV001101298 SCV001257899 uncertain significance Familial restrictive cardiomyopathy 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 Clinical Services Laboratory,Illumina RCV001101299 SCV001257900 uncertain significance Familial 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.
Color Health, Inc RCV000769740 SCV001339609 likely benign Cardiomyopathy 2018-12-10 criteria provided, single submitter clinical testing

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