ClinVar Miner

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

gnomAD frequency: 0.00001  dbSNP: rs377114166
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Total submissions: 6
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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).
Labcorp Genetics (formerly Invitae), Labcorp 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 RCV004528229 SCV004107064 uncertain significance TTN-related disorder 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.

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