Submissions for variant NM_005050.4(ABCD4):c.751C>T (p.Arg251Cys)

gnomAD frequency: 0.00150  dbSNP: rs141868117

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000423379	SCV000522426	uncertain significance	not provided	2018-03-30	criteria provided, single submitter	clinical testing	The R251C variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R251C variant is observed in 40/10,146 (0.4%) alleles from individuals of Ashkenazi Jewish background, in large population cohorts the ExAC dataset (Lek et al., 2016); it has also been identified as apparently homozygous in an apparently unaffected individual undergoing testing at GeneDx. The R251C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001083323	SCV001114770	likely benign	Methylmalonic acidemia with homocystinuria, type cblJ	2025-01-30	criteria provided, single submitter	clinical testing
Centogene AG - the Rare Disease Company	RCV001083323	SCV002059577	uncertain significance	Methylmalonic acidemia with homocystinuria, type cblJ	2018-10-29	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003959901	SCV004774924	likely benign	ABCD4-related disorder	2023-03-19	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).