Submissions for variant NM_004341.5(CAD):c.98T>G (p.Met33Arg) (rs751610198)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000520587	SCV000618435	likely pathogenic	not provided	2017-05-01	criteria provided, single submitter	clinical testing	The M33R variant in the CAD gene has been reported in the homozygous state in multiple individualswith seizures, developmental delay, anemia with anisopoikilocytosis and brain atrophy from twounrelated families of Serbian Roma origin (Koch et al., 2017). The M33R variant is not observed inlarge population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome VariantServer). The M33R variant is a non-conservative amino acid substitution, which is likely to impactsecondary 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 thisvariant is probably damaging to the protein structure/function. We interpret M33R as a likelypathogenic variant.
Institute of Human Genetics,Klinikum rechts der Isar	RCV000415540	SCV000680160	pathogenic	Epileptic encephalopathy, early infantile, 50	2017-12-09	criteria provided, single submitter	clinical testing
OMIM	RCV000415540	SCV000493912	pathogenic	Epileptic encephalopathy, early infantile, 50	2017-07-20	no assertion criteria provided	literature only