Submissions for variant NM_001267550.2(TTN):c.20027C>A (p.Ser6676Tyr)

dbSNP: rs746565627

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000521946	SCV000618871	uncertain significance	not provided	2017-06-27	criteria provided, single submitter	clinical testing	The S5432Y variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The S5432Y variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, this substitution occurs at a position that is not conserved and the majority of pathogenic variants in the TTN gene are loss of function and result from truncating variants. Additionally, the S5432Y variant is not located in the A-band nor the M-line region of titin, where the majority of pathogenic truncating variants have been reported. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
CeGaT Center for Human Genetics Tuebingen	RCV000521946	SCV004033829	uncertain significance	not provided	2023-08-01	criteria provided, single submitter	clinical testing	TTN: PM2, BP4