ClinVar Miner

Submissions for variant NM_015506.3(MMACHC):c.650A>T (p.Glu217Val)

gnomAD frequency: 0.00009  dbSNP: rs199641732
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000555947 SCV000640289 uncertain significance Cobalamin C disease 2021-08-12 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with valine at codon 217 of the MMACHC protein (p.Glu217Val). The glutamic acid residue is moderately conserved and there is a moderate physicochemical difference between glutamic acid and valine. This variant is present in population databases (rs199641732, ExAC 0.02%). This missense change has been observed in individual(s) with MMACHC-related conditions (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Mayo Clinic Laboratories, Mayo Clinic RCV001508862 SCV001715280 uncertain significance not provided 2020-05-06 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000555947 SCV002786886 uncertain significance Cobalamin C disease 2024-06-20 criteria provided, single submitter clinical testing
Ambry Genetics RCV003258864 SCV003944468 uncertain significance Inborn genetic diseases 2023-04-26 criteria provided, single submitter clinical testing The c.650A>T (p.E217V) alteration is located in exon 4 (coding exon 4) of the MMACHC gene. This alteration results from a A to T substitution at nucleotide position 650, causing the glutamic acid (E) at amino acid position 217 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV000555947 SCV004178220 uncertain significance Cobalamin C disease 2023-04-11 criteria provided, single submitter clinical testing
Natera, Inc. RCV000555947 SCV002089555 uncertain significance Cobalamin C disease 2018-04-21 no assertion criteria provided clinical testing

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