Submissions for variant NM_001276345.2(TNNT2):c.772T>G (p.Phe258Val)

dbSNP: rs730881110

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000159342	SCV000209288	uncertain significance	not provided	2017-05-10	criteria provided, single submitter	clinical testing	p.Phe248Val (TTC>GTC): c.742 T>G in exon 14 of the TNNT2 gene (NM_001001430.1). The F248V variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The F248V variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The F248V variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. Missense mutations in nearby residues (K247R, E244D) have been reported in association with HCM, supporting the functional importance of this region of the protein. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in HCM panel(s).
Color Diagnostics, LLC DBA Color Health	RCV001189395	SCV001356678	uncertain significance	Cardiomyopathy	2018-11-22	criteria provided, single submitter	clinical testing	Variant of Uncertain Significance due to insufficient evidence: This missense variant is located in the tropomyosin/actin/troponin I binding domain of the TNNT2 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant is rare in the general population and has been identified in 0/277264 chromosomes by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.
Genome-Nilou Lab	RCV003453254	SCV004181231	uncertain significance	Dilated cardiomyopathy 1D	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003453255	SCV004181232	uncertain significance	Cardiomyopathy, familial restrictive, 3	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003453253	SCV004181233	uncertain significance	Hypertrophic cardiomyopathy 2	2023-04-11	criteria provided, single submitter	clinical testing