ClinVar Miner

Submissions for variant NM_015702.3(MMADHC):c.746A>G (p.Tyr249Cys) (rs118204046)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001378885 SCV001576573 likely pathogenic Methylmalonic acidemia with homocystinuria cblD 2020-09-11 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 249 of the MMADHC protein (p.Tyr249Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs118204046, ExAC 0.04%). This variant has been observed in individual(s) with cobalamin D deficiency (PMID: 22156578, 25155779, 18385497). ClinVar contains an entry for this variant (Variation ID: 763). Experimental studies have shown that this variant affects MMADHC protein function (PMID: 22156578, 18385497). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000000799 SCV000020949 pathogenic Homocystinuria, cblD type, variant 1 2008-04-03 no assertion criteria provided literature only

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