Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001377466 | SCV001574803 | likely pathogenic | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2017-04-26 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Likely Pathogenic. 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). ClinVar contains an entry for this variant (Variation ID: 202384). This sequence change affects a donor splice site in intron 347 of the TTN gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |
Ambry Genetics | RCV002367860 | SCV002664407 | uncertain significance | Cardiovascular phenotype | 2022-06-06 | criteria provided, single submitter | clinical testing | The c.69709+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 174 of the TTN gene. Exon 174 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 alteration disrupts the canonical splice site and is expected to cause aberrant splicing. However, although direct evidence is unavailable, this alteration is predicted to result in an in-frame transcript that is not expected to trigger nonsense-mediated mRNA decay. The exact functional effect of the predicted splice impact is unknown. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |