Submissions for variant NM_001267550.2(TTN):c.47574G>C (p.Glu15858Asp)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002419852	SCV002718746	uncertain significance	Cardiovascular phenotype	2020-05-19	criteria provided, single submitter	clinical testing	The p.E6793D variant (also known as c.20379G>C), located in coding exon 81 of the TTN gene, results from a G to C substitution at nucleotide position 20379. The glutamic acid at codon 6793 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is highly 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.
GeneDx	RCV002508361	SCV002817975	uncertain significance	not provided	2022-06-29	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on splicing; Located in the A-band region of TTN in which the majority of loss of function variants have been associated with autosomal dominant titinopathies (Herman et al., 2012); Has not been previously published as pathogenic or benign to our knowledge
PreventionGenetics, part of Exact Sciences	RCV004545323	SCV004765547	uncertain significance	TTN-related disorder	2023-12-20	no assertion criteria provided	clinical testing	The TTN c.47574G>C variant is predicted to result in the amino acid substitution p.Glu15858Asp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0045% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.