ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.107460_107463dup (p.Gln35822fs)

dbSNP: rs886042246
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000319760 SCV000332866 uncertain significance not provided 2015-07-21 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000464716 SCV000542323 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2J 2017-04-26 criteria provided, single submitter clinical testing This sequence change inserts 4 nucleotides in exon 362 of the TTN mRNA (c.107460_107463dupAGTC), causing a frameshift at codon 35822. This creates a premature translational stop signal (p.Gln35822Serfs*21) and is expected to result in an absent or disrupted protein product. This variant is found in the M-band of this gene. While this particular variant has not been reported in the literature, truncating variants in the M-band of TTN previously reported in patients affected with various forms of myopathy and muscular dystrophy (PMID: 18948003, 23975875, 24395473). For these reasons, this variant has been classified as Likely Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001378679 SCV001576302 likely pathogenic Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2022-07-12 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln35822Serfs*21) in the TTN gene. While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein. This variant is not present in population databases (gnomAD no frequency). 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: 404666). 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), but have not been definitively shown to cause cardiomyopathy (PMID: 25589632). 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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