Submissions for variant NM_000255.4(MMUT):c.1867G>A (p.Gly623Arg) (rs121918254)

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000427444	SCV000520995	pathogenic	not provided	2017-01-31	criteria provided, single submitter	clinical testing	The G623R variant in the MUT gene has previously been reported in association with methylmalonic acidemia (MMA) in several unrelated individuals who were homozygous for G623R or heterozygous for G623R and another variant in the MUT gene (Qureshi et al., 1994; Worgan et al., 2006; Cosson et al., 2009). This variant is reported to be a common variant in individuals of African descent and functional analysis of G623R found that it is associated with significantly reduced enzyme activity compared to wild-type (Worgan et al., 2006; Janata et al., 1997). The G623R 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. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore we interpret G623R to be a pathogenic variant.
OMIM	RCV000001961	SCV000022119	pathogenic	METHYLMALONIC ACIDURIA, mut(0) TYPE	1994-04-01	no assertion criteria provided	literature only
GeneReviews	RCV000203390	SCV000258505	pathogenic	Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency	2016-01-07	no assertion criteria provided	literature only
Counsyl	RCV000203390	SCV001132252	likely pathogenic	Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency	2017-03-17	no assertion criteria provided	clinical testing