ClinVar Miner

Submissions for variant NM_000143.3(FH):c.1138A>G (p.Met380Val) (rs587778362)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000554866 SCV000632436 uncertain significance Fumarase deficiency 2018-12-18 criteria provided, single submitter clinical testing This sequence change replaces methionine with valine at codon 380 of the FH protein (p.Met380Val). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and valine. This variant is present in population databases (rs587778362, ExAC 0.01%) but has not been reported in the literature in individuals with a FH-related disease. ClinVar contains an entry for this variant (Variation ID: 134417). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000567053 SCV000673365 uncertain significance Hereditary cancer-predisposing syndrome 2017-06-15 criteria provided, single submitter clinical testing Insufficient evidence;In silico models in agreement (benign)
ITMI RCV000121093 SCV000085261 not provided not specified 2013-09-19 no assertion provided reference population

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