ClinVar Miner

Submissions for variant NM_015506.3(MMACHC):c.1A>G (p.Met1Val) (rs758477536)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000440436 SCV000520985 pathogenic not provided 2017-01-04 criteria provided, single submitter clinical testing The c.1 A>G pathogenic variant has been reported previously in association with cblC deficiency (Lerner-Ellis et al., 2009; Wang et al., 2012). The c.1 A>G variant alters the initiator Methionine codon, and the resultant protein would be described as p.Met1?" using a question mark to signify that it is not known if the loss of Met1 means that all protein translation is completely prevented or if an abnormal protein is produced using an alternate Met."
Counsyl RCV000666093 SCV000790333 pathogenic Methylmalonic acidemia with homocystinuria 2017-03-15 criteria provided, single submitter clinical testing
Invitae RCV000666093 SCV000950670 pathogenic Methylmalonic acidemia with homocystinuria 2018-08-27 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the MMACHC mRNA. The next in-frame methionine is located at codon 58. This variant is present in population databases (rs758477536, ExAC 0.006%). Disruption of the initiator codon has been been observed has been observed to be homozygous or in combination with another MMACHC variant in individuals affected with methylmalonic aciduria and homocystinuria (PMID: 17768669, 16311595, 28693988, 19760748). ClinVar contains an entry for this variant (Variation ID: 381577). For these reasons, this variant has been classified as Pathogenic.

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