Submissions for variant NM_001267550.2(TTN):c.66707A>G (p.Asn22236Ser)

gnomAD frequency: 0.00001  dbSNP: rs771424887

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000184740	SCV000237446	uncertain significance	not specified	2013-02-26	criteria provided, single submitter	clinical testing	Missense variants in the TTN gene are considered 'unclassified' if they are not previously reported in the literature and do not have >1% frequency in the population to be considered a polymorphism. Research indicates that truncating mutations in the TTN gene are expected to account for approximately 25% of familial and 18% of sporadic idiopathic DCM; however, truncating variants in the TTN gene have been reported in approximately 3% of reported control alleles. There has been little investigation into non-truncating variants. (Herman D et al. Truncations of titin causing dilated cardiomyopathy. N Eng J Med 366:619-628, 2012) The variant is found in DCM panel(s).
Ambry Genetics	RCV002354505	SCV002621930	uncertain significance	Cardiovascular phenotype	2020-09-17	criteria provided, single submitter	clinical testing	The p.N13171S variant (also known as c.39512A>G), located in coding exon 143 of the TTN gene, results from an A to G substitution at nucleotide position 39512. The asparagine at codon 13171 is replaced by serine, 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.