ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.66187G>C (p.Val22063Leu)

gnomAD frequency: 0.00004  dbSNP: rs768057735
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000724792 SCV000228406 uncertain significance not provided 2015-05-05 criteria provided, single submitter clinical testing
GeneDx RCV000724792 SCV000577017 uncertain significance not provided 2017-04-12 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the TTN gene. While the V20422L variant has not been published as pathogenic or been reported as benign to our knowledge, it has been classified as a variant of uncertain significance (reported as V22063L using alternate nomenclature) by another clinical laboratory in ClinVar (SCV000228406.3; Landrum et al., 2016). This variant is observed in 12/65,868 (0.02%) alleles from individuals of European ancestry in the ExAC dataset (Lek et al., 2016; Exome Variant Server). The V20422L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to valine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the missense substitution is damaging to the protein structure/function. Nevertheless, the V20422L variant is predicted to strengthen a potential downstream cryptic splice acceptor site, which may lead to abnormal gene splicing. Guanine (G) is not conserved across species but only purines are observed as wild-type at this position. In the absence of functional mRNA studies, the physiological consequence of this variant cannot be precisely determined.
Invitae RCV000555829 SCV000643542 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2018-01-05 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000724792 SCV001152802 uncertain significance not provided 2018-05-01 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002500489 SCV002814736 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 2022-04-14 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000724792 SCV003822297 uncertain significance not provided 2020-02-12 criteria provided, single submitter clinical testing

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