ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.56792G>A (p.Trp18931Ter)

dbSNP: rs1060500526
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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 RCV000458129 SCV000542886 likely pathogenic Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2024-07-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp18931*) 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: 405009). 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). 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.
Ambry Genetics RCV003362790 SCV004053250 likely pathogenic Cardiovascular phenotype 2024-02-22 criteria provided, single submitter clinical testing The c.29597G>A (p.W9866*) alteration, located in exon 119 (coding exon 118) of the TTN gene, consists of a G to A substitution at nucleotide position 29597. This changes the amino acid from a tryptophan (W) to a stop codon at amino acid position 9866. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This exon is located in the A-band region of the N2-B isoform of the titin protein and is constitutively expressed in TTN transcripts (percent spliced in or PSI 100%). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the available evidence, this alteration is classified as likely pathogenic.

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