ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.106019del (p.Gly35340fs)

dbSNP: rs727504482
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV003326384 SCV004033790 pathogenic not provided 2023-08-01 criteria provided, single submitter clinical testing TTN: PVS1, PM2
GeneDx RCV003326384 SCV004036843 pathogenic not provided 2023-09-15 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Located in the M-line region of TTN in which the majority of loss of function variants have been associated with autosomal recessive titinopathies (Carmignac et al., 2007); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 17444505, 32778822, 23975875)
Labcorp Genetics (formerly Invitae), Labcorp RCV003765466 SCV004568979 likely pathogenic Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2023-12-06 criteria provided, single submitter clinical testing While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 652 amino acid(s) of the TTN protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with autosomal recessive centronuclear myopathy and/or dilated cardiomyopathy (PMID: 23975875; Invitae). This variant is also known as p.G32772fs. ClinVar contains an entry for this variant (Variation ID: 242624). This variant is located in the M band of TTN (PMID: 25589632). Truncating variants in this region have been previously reported in individuals affected with autosomal recessive myopathy and muscular dystrophy (PMID: 18948003, 23975875, 24395473). Truncating variants in this region have also been identified in individuals affected with autosomal dominant dilated cardiomyopathy and/or cardio-related conditions (PMID: 27869827, 32964742). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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