Submissions for variant NM_001267550.2(TTN):c.12175G>T (p.Gly4059Cys)

gnomAD frequency: 0.00001  dbSNP: rs377114166

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000041087	SCV000064778	uncertain significance	not specified	2013-02-12	criteria provided, single submitter	clinical testing	The Gly3821Lys variant in TTN has not been described in the literature nor previ ously identified by our laboratory. This variant has been identified in 1/8208 o f European American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS/; dbSNP). Computational analyses are limited or unavailable for this variant. In summary, additional information is needed to fully assess the clinical significance of the Gly3821Lys variant.
GeneDx	RCV000041087	SCV000238172	uncertain significance	not specified	2014-07-15	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 CARDIOMYOPATHY panel(s).
Invitae	RCV000643723	SCV000765410	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-11-14	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002504918	SCV002816610	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J; Tibial muscular dystrophy; Myopathy, myofibrillar, 9, with early respiratory failure; Early-onset myopathy with fatal cardiomyopathy; Hypertrophic cardiomyopathy 9	2021-11-12	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003149667	SCV003838617	uncertain significance	Cardiomyopathy	2022-01-17	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003415780	SCV004107064	uncertain significance	TTN-related condition	2022-12-12	criteria provided, single submitter	clinical testing	The TTN c.12175G>T variant is predicted to result in the amino acid substitution p.Gly4059Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-179605785-C-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.