ClinVar Miner

Submissions for variant NM_005957.4(MTHFR):c.1667C>T (p.Pro556Leu) (rs747712448)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000558638 SCV000641854 uncertain significance Homocysteinemia due to MTHFR deficiency 2017-07-11 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 556 of the MTHFR protein (p.Pro556Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs747712448, ExAC 0.01%). This variant has been observed on opposite chromosomes (in trans) from an MTHFR pathogenic variant in an individual affected with homocystinuria (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. Therefore, it has been classified as a Variant of Uncertain Significance.

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