ClinVar Miner

Submissions for variant NM_000143.4(FH):c.909G>C (p.Leu303Phe)

gnomAD frequency: 0.00001  dbSNP: rs1659857850
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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 RCV002556354 SCV002180806 uncertain significance not provided 2021-09-24 criteria provided, single submitter clinical testing This sequence change replaces leucine with phenylalanine at codon 303 of the FH protein (p.Leu303Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with FH-related conditions. 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.
Ambry Genetics RCV003339818 SCV004059163 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-11 criteria provided, single submitter clinical testing The p.L303F variant (also known as c.909G>C), located in coding exon 7 of the FH gene, results from a G to C substitution at nucleotide position 909. The leucine at codon 303 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV003464232 SCV004197308 uncertain significance Fumarase deficiency 2023-10-16 criteria provided, single submitter clinical testing

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