ClinVar Miner

Submissions for variant NM_000143.4(FH):c.763G>A (p.Val255Ile)

gnomAD frequency: 0.00001  dbSNP: rs752144845
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001026656 SCV001189084 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-08 criteria provided, single submitter clinical testing The p.V255I variant (also known as c.763G>A), located in coding exon 6 of the FH gene, results from a G to A substitution at nucleotide position 763. The valine at codon 255 is replaced by isoleucine, 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.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV002552415 SCV002010129 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002552415 SCV002185650 uncertain significance not provided 2022-10-06 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 255 of the FH protein (p.Val255Ile). This variant is present in population databases (rs752144845, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with FH-related conditions. ClinVar contains an entry for this variant (Variation ID: 827167). 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 not 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.
Natera, Inc. RCV001273817 SCV001457345 uncertain significance Fumarase deficiency 2020-09-16 no assertion criteria provided clinical testing

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