ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.67282G>T (p.Val22428Leu)

gnomAD frequency: 0.00001  dbSNP: rs794729483
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV003150071 SCV003837982 likely benign Cardiomyopathy 2021-12-29 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004689660 SCV005185640 uncertain significance not specified 2024-05-17 criteria provided, single submitter clinical testing Variant summary: TTN c.59578G>T (p.Val19860Leu) results in a conservative amino acid change located in the A-band domain of the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 248352 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.59578G>T in individuals affected with Limb-Girdle Muscular Dystrophy, Type 2J and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 202808). Based on the evidence outlined above, the variant was classified as uncertain significance.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV004689660 SCV006065195 likely benign not specified 2025-04-09 criteria provided, single submitter clinical testing
GeneDx RCV000184746 SCV000237453 not provided not provided 2013-01-15 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).

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