ClinVar Miner

Submissions for variant NM_000143.3(FH):c.1421C>G (p.Thr474Arg) (rs369802820)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000381370 SCV000356658 likely benign Multiple cutaneous leiomyomas 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000296074 SCV000356659 likely benign Multiple Cutaneous and Uterine Leiomyomas 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000332300 SCV000356660 likely benign Fumarase deficiency 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000332300 SCV000544240 uncertain significance Fumarase deficiency 2018-11-01 criteria provided, single submitter clinical testing This sequence change replaces threonine with arginine at codon 474 of the FH protein (p.Thr474Arg). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and arginine. This variant is present in population databases (rs369802820, ExAC 0.1%) but has not been reported in the literature in individuals with a FH-related disease. 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: "Benign"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. Because it is found in the population at an appreciable frequency, this variant is not anticipated to cause disease. However, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034487 SCV000043259 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.

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