Submissions for variant NM_000390.4(CHM):c.877C>T (p.Arg293Ter)

dbSNP: rs132630266

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000078687	SCV000110547	pathogenic	not provided	2013-10-29	criteria provided, single submitter	clinical testing
GeneDx	RCV000078687	SCV000680505	pathogenic	not provided	2017-12-12	criteria provided, single submitter	clinical testing	The R293X variant in the CHM gene has been reported previously (also as R294X due to alternate nomenclature) in multiple unrelated patients with choroideremia (van Bokhoven et al., 1994; Jolly et al., 2015; McLaren et al., 2015; Sanchez-Alcudia et al., 2016). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R293X variant is not observed in large population cohorts (Lek et al., 2016). We interpret R293X as a pathogenic variant.
CeGaT Center for Human Genetics Tuebingen	RCV000078687	SCV001248391	pathogenic	not provided	2017-08-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000078687	SCV001377144	pathogenic	not provided	2024-11-05	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg293*) in the CHM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CHM are known to be pathogenic (PMID: 9067750, 23811034). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with choroidemia (PMID: 26133251, 28559085). ClinVar contains an entry for this variant (Variation ID: 11154). 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.
Ophthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel	RCV000011904	SCV004030378	pathogenic	Choroideremia	2023-07-24	criteria provided, single submitter	research	Clinical significance based on ACMG v2.0
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV004814884	SCV005068433	pathogenic	Retinal dystrophy	2023-01-01	criteria provided, single submitter	clinical testing
OMIM	RCV000011904	SCV000032137	pathogenic	Choroideremia	1994-07-01	no assertion criteria provided	literature only
Sharon lab, Hadassah-Hebrew University Medical Center	RCV000011904	SCV001160981	pathogenic	Choroideremia	2019-06-23	no assertion criteria provided	research
GeneReviews	RCV000011904	SCV002012455	not provided	Choroideremia		no assertion provided	literature only