ClinVar Miner

Submissions for variant NM_000143.3(FH):c.1157A>G (p.Gln386Arg) (rs750447792)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000469317 SCV000544290 likely pathogenic Fumarase deficiency 2018-06-06 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 386 of the FH protein (p.Gln386Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is not present in population databases (ExAC no frequency). This sequence change has been reported in individuals with a personal and family history of hereditary leiomyomatosis and renal cell cancer (HLRCC) (PMID: 21398687, 25292446). This variant is also known as c.1028A>G (p.Gln343Arg) in the literature. ClinVar contains an entry for this variant (Variation ID: 405939). In an experimental study, FH enzymatic activity was shown to be decreased in a lymphoblastoid cell line carrying this variant (PMID: 21398687). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Ambry Genetics RCV000562894 SCV000664717 likely pathogenic Hereditary cancer-predisposing syndrome 2017-01-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation

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