ClinVar Miner

Submissions for variant NM_001276345.2(TNNT2):c.775G>A (p.Asp259Asn) (rs141805127)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000172136 SCV000051078 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
GeneDx RCV000172136 SCV000209260 uncertain significance not provided 2020-10-02 criteria provided, single submitter clinical testing Identified by exome sequencing as a variant of uncertain significance in a cohort of individuals with cardiac disease in the literature (Ng et al., 2013); however, specific information was not provided about the number of patients with this variant, their phenotype, or presence/absence of other variants; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30847666, 30165862, 23861362)
Invitae RCV000466482 SCV000541934 uncertain significance Familial hypertrophic cardiomyopathy 2; Left ventricular noncompaction 6; Familial restrictive cardiomyopathy 3 2020-10-30 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 249 of the TNNT2 protein (p.Asp249Asn). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs141805127, ExAC 0.02%). This variant has been observed in an individual affected with cardiomyopathy (PMID: 30165862). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000620239 SCV000739979 uncertain significance Cardiovascular phenotype 2019-05-17 criteria provided, single submitter clinical testing The p.D249N variant (also known as c.745G>A), located in coding exon 13 of the TNNT2 gene, results from a G to A substitution at nucleotide position 745. The aspartic acid at codon 249 is replaced by asparagine, an amino acid with highly similar properties. This variant has been reported in one individual from a cardiomyopathy cohort and as a secondary cardiac variant in an exome cohort; however clinical details were limited (Ng D et al. Circ Cardiovasc Genet, 2013 Aug;6:337-46; Lu C et al. J Transl Med, 2018 08;16:241). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Mendelics RCV000986502 SCV001135515 uncertain significance Familial hypertrophic cardiomyopathy 2 2019-05-28 criteria provided, single submitter clinical testing
Color Health, Inc RCV001177367 SCV001341565 uncertain significance Cardiomyopathy 2019-11-22 criteria provided, single submitter clinical testing

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