ClinVar Miner

Submissions for variant NM_174917.5(ACSF3):c.1075G>A (p.Glu359Lys) (rs150487794)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000185748 SCV000331886 uncertain significance not provided 2015-06-10 criteria provided, single submitter clinical testing
GeneDx RCV000185748 SCV000238677 pathogenic not provided 2017-03-21 criteria provided, single submitter clinical testing This variant is denoted p.Glu359Lys at the protein level, c.1075 G>A at the cDNA level, and results in the replacement of a Glutamic acid with a Lysine (GAG>AAG) in exon 6 of the ACSF3 gene (NM_174917.3). Mutations in the ACSF3 gene are associated with the autosomal recessive disorder combined malonic and methylmalonic aciduria (CMAMMA).The E359K missense mutation in the ACSF3 gene has been reported previously in association with combined malonic and methylmalonic aciduria (CMAMMA) (Alfares et al., 2011). The variant is found in MMA-MET panel(s).
Invitae RCV000024132 SCV000771501 pathogenic Combined malonic and methylmalonic aciduria 2018-11-20 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 359 of the ACSF3 protein (p.Glu359Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs150487794, ExAC 0.1%). This variant has been observed in individuals and families affected with combined malonic and methylmalonic aciduria and to segregate with disease (PMID: 21785126, 26915364, 29858964, 21841779, Invitae). ClinVar contains an entry for this variant (Variation ID: 31136). 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. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000024132 SCV000045423 pathogenic Combined malonic and methylmalonic aciduria 2011-08-14 no assertion criteria provided literature only

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