ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.105083C>T (p.Thr35028Met)

gnomAD frequency: 0.00001  dbSNP: rs56001826
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001852408 SCV002135727 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2023-07-31 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant is located in the M band of TTN (PMID: 25589632). Variants in this region may be relevant for neuromuscular disorders, but have not been definitively shown to cause cardiomyopathy (PMID: 23975875). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 35028 of the TTN protein (p.Thr35028Met). This variant is present in population databases (rs56001826, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with TTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 203090). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown.
Fulgent Genetics, Fulgent Genetics RCV002492845 SCV002791237 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 2021-08-23 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004528967 SCV004112612 uncertain significance TTN-related disorder 2023-02-08 criteria provided, single submitter clinical testing The TTN c.105083C>T variant is predicted to result in the amino acid substitution p.Thr35028Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0056% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-179396259-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
GeneDx RCV000185113 SCV000237938 not provided not provided 2013-09-13 no assertion provided 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).
Clinical Genetics, Academic Medical Center RCV000185113 SCV001918024 uncertain significance not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000185113 SCV001932082 uncertain significance not provided no assertion criteria provided clinical testing

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