Submissions for variant NM_001267550.2(TTN):c.68456T>C (p.Met22819Thr)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002333022	SCV002627161	uncertain significance	Cardiovascular phenotype	2020-01-10	criteria provided, single submitter	clinical testing	The p.M13754T variant (also known as c.41261T>C), located in coding exon 149 of the TTN gene, results from a T to C substitution at nucleotide position 41261. The methionine at codon 13754 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx	RCV004591895	SCV005078349	uncertain significance	not provided	2023-04-06	criteria provided, single submitter	clinical testing	Reported in two alleles from a large cohort of individuals with skeletal muscle diseases, however individual clinical and segregation information was not provided (Savarese et al., 2020); Not observed at significant frequency in large population cohorts (gnomAD); Missense variant in a gene in which most reported pathogenic variants are truncating/loss of function; 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); This variant is associated with the following publications: (PMID: 32039858)