Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001063107 | SCV001227941 | likely pathogenic | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2021-09-10 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002327339 | SCV002630341 | likely pathogenic | Cardiovascular phenotype | 2021-01-27 | criteria provided, single submitter | clinical testing | The c.42227_42231delGCCCTins10 variant, located in coding exon 152 of the TTN gene, results from the deletion of 5 nucleotides and insertion of 10 nucleotides (AAAAGGACCC) causing a translational frameshift with a predicted alternate stop codon (p.G14076Efs*38). 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 (referred to as NM_001267550:c.69422_69426delinsAAAAGGACCC, p.Gly23141Glufs*38) has been detected in an individual from a dilated cardiomyopathy (DCM) cohort (Ramchand J et al. J Am Heart Assoc. 2020 01;9(2):e013346). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. While truncating variants in TTN are present in 1-3% of the general population, truncating variants in the A-band are the most common cause of DCM (Herman DS et al. N. Engl. J. Med., 2012 Feb;366:619-28; Roberts AM et al. Sci Transl Med, 2015 Jan;7:270ra6). TTN truncating variants encoded in constitutive exons (PSI >90%) have been found to be significantly associated with DCM regardless of their position in titin (Schafer S et al. Nat. Genet., 2017 01;49:46-53). As such, this alteration is classified as likely pathogenic. |