Submissions for variant NM_000543.5(SMPD1):c.1118del (p.Pro373fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Myriad Genetics, Inc.	RCV002308414	SCV002603347	likely pathogenic	Niemann-Pick disease, type B; Niemann-Pick disease, type A	2022-01-02	criteria provided, single submitter	clinical testing	NM_000543.4(SMPD1):c.1118delC(P373Hfs*12) is expected to be pathogenic in the context of Niemann-Pick disease, SMPD1-related. This variant is predicted to lead to an abnormal or absent protein product due to the creation of a premature termination codon in SMPD1, a gene where loss-of-function variants are known to be pathogenic. Please note: this variant was assessed in the context of healthy population screening.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002308414	SCV003232400	pathogenic	Niemann-Pick disease, type B; Niemann-Pick disease, type A	2022-08-29	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with SMPD1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Pro373Hisfs*12) in the SMPD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SMPD1 are known to be pathogenic (PMID: 12369017, 15221801).