Submissions for variant NM_001943.5(DSG2):c.1109dup (p.Thr371fs)

dbSNP: rs1555627118

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000603286	SCV000711722	uncertain significance	not specified	2017-12-07	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Pathogenic. The p.Thr371fs variant in DSG2 has not been previously reported in individuals with cardiomyopa thy and was absent from large population studies. This variant is predicted to c ause a frameshift, which alters the protein?s amino acid sequence beginning at p osition 371 and leads to a premature termination codon 19 amino acids downstream . This alteration is then predicted to lead to a truncated or absent protein. Fr ameshift and other loss of function variants in DSG2 gene have been reported in individuals with ARVC. In summary, while there is some suspicion for a pathogeni c role, the clinical significance of the p.Thr371fs variant is uncertain.
GeneDx	RCV001561033	SCV001783553	likely pathogenic	not provided	2023-02-16	criteria provided, single submitter	clinical testing	Reported in an individual undergoing whole exome sequencing in published literature (Sapp et al., 2018); although the indications for testing and follow-up cardiac evaluations were not described; Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 30122538)