ClinVar Miner

Submissions for variant NM_000429.3(MAT1A):c.790C>T (p.Arg264Cys) (rs118204005)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000001269 SCV000816635 pathogenic Hepatic methionine adenosyltransferase deficiency 2018-04-18 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 264 of the MAT1A protein (p.Arg264Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in combination with another MAT1A variant in individuals affected with the autosomal recessive form of hypermethioninemia (PMID: 10677294, 15935930, 26289392). ClinVar contains an entry for this variant (Variation ID: 1210). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. A different missense substitution at this codon (p.Arg264His) has been determined to be pathogenic and causes an autosomal dominant form of hypermethioninemia (PMID: 9042912, 23430947, 24445979, 11278456, 23425511). This suggests that the arginine residue is critical for MAT1A protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000001269 SCV000021419 pathogenic Hepatic methionine adenosyltransferase deficiency 2000-02-01 no assertion criteria provided literature only

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