ClinVar Miner

Submissions for variant NM_000143.4(FH):c.1169A>G (p.Asn390Ser)

dbSNP: rs1178007598
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Bruce Lefroy Centre, Murdoch Childrens Research Institute RCV001072142 SCV001235708 likely pathogenic Fumarase deficiency 2020-01-01 criteria provided, single submitter research PM2, PM3, PP3, PP4
GeneDx RCV003128750 SCV003805818 uncertain significance not provided 2022-08-22 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Published functional studies demonstrate: 25% residual FH enzyme activity (Stutterd et al., 2021); This variant is associated with the following publications: (PMID: 33604570)
Invitae RCV003128750 SCV004555005 uncertain significance not provided 2023-06-11 criteria provided, single submitter clinical testing Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FH protein function. 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. ClinVar contains an entry for this variant (Variation ID: 864859). This missense change has been observed in individual(s) with clinical features of FH-related conditions (PMID: 33604570). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 390 of the FH protein (p.Asn390Ser).

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