Submissions for variant NM_001267550.2(TTN):c.61067del (p.Pro20356fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Diagnostics Centre, Carl Von Ossietzky University Oldenburg	RCV004566516	SCV005049563	likely pathogenic	Dilated cardiomyopathy 1G	2023-05-09	no assertion criteria provided	clinical testing	The variant TTN:c.61067del, p.(Pro20356Hisfs*8), which is located in the coding exon 304 of the TTN gene, results from a deletion of a guanine at nucleotide position 61067. The variant causes a frameshift that results in the replace of a proline residue by a hystidine at protein position 20356, followed by a premature translation stop codon after eight amino acids. The variant affects and exon (304/363) that is present in biologically relevant transcripts and it is predicted to cause protein truncation/absent due to non-sense mediated decay in a gene where loss of function is a known mechanism of disease. The change is located in the front third of the A-band of titin. Heterozygous alterations affecting the A-band are associated with cardiomyopathies (PMID: 32815318). The variant is classified as very rare in the overall population (no carriers in gnomAD, v4.0.0). In summary, this variant is classified as Likely Pathogenic.
Cardiogenetics and Myogenetics Molecular and Cellular Functional Unit, Aphp Sorbonne University-Hopital Pitie Salpetriere	RCV004566516	SCV005374912	likely pathogenic	Dilated cardiomyopathy 1G	2024-01-06	no assertion criteria provided	clinical testing