ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.51234_51237dup (p.Leu17080fs)

dbSNP: rs1553693444
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000526677 SCV000642434 likely pathogenic Dilated cardiomyopathy 1G 2017-03-21 criteria provided, single submitter clinical testing This sequence change inserts 4 nucleotides in exon 271 of the TTN mRNA (c.51234_51237dupAATT), causing a frameshift at codon 17080. This creates a premature translational stop signal (p.Leu17080Asnfs*23) and is expected to result in a disrupted protein product. This variant is found in the A-band of this gene. While this particular variant has not been reported in the literature, truncating variants in the A-band of TTN are significantly overrepresented in patients with dilated cardiomyopathy and are considered to be likely pathogenic for the disease (PMID: 25589632). For these reasons, this variant has been classified as Likely Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001377202 SCV001574472 likely pathogenic Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2022-01-05 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu17080Asnfs*23) in the TTN gene. While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein. 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. This variant is located in the A band of TTN (PMID: 25589632). Truncating variants in this region are significantly overrepresented in patients affected with dilated cardiomyopathy (PMID: 25589632). Truncating variants in this region have also been reported in individuals affected with autosomal recessive centronuclear myopathy (PMID: 23975875). ClinVar contains an entry for this variant (Variation ID: 466634). This variant has not been reported in the literature in individuals affected with TTN-related conditions.

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