Submissions for variant NM_001371279.1(REEP1):c.182G>A (p.Trp61Ter)

dbSNP: rs1558898568

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000760593	SCV000890484	pathogenic	not provided	2018-06-14	criteria provided, single submitter	clinical testing	The W61X nonsense variant in the REEP1 gene1 has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (Stenson et al., 2014). Additionally, the W61X variant is not observed in large population cohorts (Lek et al., 2016). The presence of this pathogenic variant is consistent with the diagnosis of a REEP1-related disorder in this individual.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000760593	SCV001446439	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001855928	SCV002234139	pathogenic	Hereditary spastic paraplegia 31	2021-11-24	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with REEP1-related conditions. This sequence change creates a premature translational stop signal (p.Trp61*) in the REEP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in REEP1 are known to be pathogenic (PMID: 18321925, 18644145, 22703882). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 620230). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV001855928	SCV005418192	pathogenic	Hereditary spastic paraplegia 31		criteria provided, single submitter	clinical testing	PM2_Supporting+PVS1+PP4
Solve-RD Consortium	RCV001855928	SCV005091561	likely pathogenic	Hereditary spastic paraplegia 31	2022-06-01	no assertion criteria provided	provider interpretation	Variant confirmed as disease-causing by referring clinical team