ClinVar Miner

Submissions for variant NM_000143.3(FH):c.1013T>C (p.Ile338Thr) (rs201975537)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000575122 SCV000673381 uncertain significance Hereditary cancer-predisposing syndrome 2016-07-20 criteria provided, single submitter clinical testing Insufficient evidence
Invitae RCV001061733 SCV001226486 uncertain significance Fumarase deficiency 2019-05-13 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 338 of the FH protein (p.Ile338Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs201975537, ExAC 0.05%). This variant has not been reported in the literature in individuals with FH-related disease. ClinVar contains an entry for this variant (Variation ID: 134416). 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. 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.
ITMI RCV000121092 SCV000085260 not provided not specified 2013-09-19 no assertion provided reference population

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