ClinVar Miner

Submissions for variant NM_000143.4(FH):c.685A>G (p.Ile229Val)

gnomAD frequency: 0.00001  dbSNP: rs764065194
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002535515 SCV000960993 uncertain significance not provided 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 229 of the FH protein (p.Ile229Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs764065194, ExAC 0.006%). This variant has not been reported in the literature in individuals affected with FH-related conditions. 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 tolerated. 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.
Ambry Genetics RCV004029034 SCV005032743 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-19 criteria provided, single submitter clinical testing The p.I229V variant (also known as c.685A>G), located in coding exon 5 of the FH gene, results from an A to G substitution at nucleotide position 685. The isoleucine at codon 229 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly 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.
Natera, Inc. RCV000820286 SCV001458376 uncertain significance Fumarase deficiency 2020-09-16 no assertion criteria provided clinical testing

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