Submissions for variant NM_001267550.2(TTN):c.53918del (p.Gly17973fs)

dbSNP: rs1486129583

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Loeys Lab, Universiteit Antwerpen	RCV001375659	SCV001572587	pathogenic	Primary dilated cardiomyopathy	2021-02-26	criteria provided, single submitter	clinical testing	This sequence change results in a truncating variant of the TTN gene (p.(Gly17973Glufs*18))The variant is present in population databases such as gnomAD (1/107016) . The variant has been described before as a Dutch Founder variant (PMID: 31112426) . Functional studies have not been performed. However truncating and frameshift mutations in TTN are a well-known mechanism for dilated cardiomyopathy (PMID: 22335739) (PVS1). The variant is located in the A-band of the titin-protein which is a known hotspot for pathogenic variants (PM1). This variant was identified and co-segregated with DCM in distinct families with DCM (PP1). In conclusion this variant was classified as pathogenic according to ACMG-guidelines (PVS1, PM1, PP1).
Clinical Genetics, Academic Medical Center	RCV001699536	SCV001920214	pathogenic	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001699536	SCV001928543	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001699536	SCV001957302	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001699536	SCV001972539	pathogenic	not provided		no assertion criteria provided	clinical testing