ClinVar Miner

Submissions for variant NM_000143.4(FH):c.294C>G (p.Ile98Met)

gnomAD frequency: 0.00001  dbSNP: rs1573886484
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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 RCV001017627 SCV001178735 uncertain significance Hereditary cancer-predisposing syndrome 2019-07-13 criteria provided, single submitter clinical testing The p.I98M variant (also known as c.294C>G), located in coding exon 3 of the FH gene, results from a C to G substitution at nucleotide position 294. The isoleucine at codon 98 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV003104006 SCV002120342 uncertain significance not provided 2021-06-05 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). 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. 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. This variant has not been reported in the literature in individuals with FH-related conditions. ClinVar contains an entry for this variant (Variation ID: 822345). This sequence change replaces isoleucine with methionine at codon 98 of the FH protein (p.Ile98Met). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and methionine.
Natera, Inc. RCV001274350 SCV001458386 uncertain significance Fumarase deficiency 2020-09-16 no assertion criteria provided clinical testing

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