Submissions for variant NM_002772.3(TMPRSS15):c.1437dup (p.Asn480Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Breakthrough Genomics, Breakthrough Genomics	RCV004596709	SCV005088895	pathogenic	Enterokinase deficiency	2021-04-16	criteria provided, single submitter	clinical testing	This variant is predicted to cause premature termination of the protein and the resultant protein will likely to lack complement component C1r-like domain (C1r/s), meprin-like domain (MAM), macrophage scavenger receptor-like domain (MSCR) and serine protease domain of the protein [PMID: 33061943]; this will likely result in loss-of-function. Due to the introduction of a premature stop codon, this aberrant transcript will likely be targeted by the nonsense-mediated mRNA decay (NMD) mechanism [PMID: 15040442]. The identified variant has not been previously reported in the literature.
Labcorp Genetics (formerly Invitae), Labcorp	RCV005102058	SCV005827164	pathogenic	not provided	2024-11-21	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Asn480*) in the TMPRSS15 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TMPRSS15 are known to be pathogenic (PMID: 11719902). This variant is present in population databases (rs755690856, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with TMPRSS15-related conditions. For these reasons, this variant has been classified as Pathogenic.