ClinVar Miner

Submissions for variant NM_000143.4(FH):c.35G>T (p.Arg12Leu)

gnomAD frequency: 0.00006  dbSNP: rs367826177
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001771986 SCV000829720 likely benign not provided 2024-08-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV001020691 SCV001182201 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-06 criteria provided, single submitter clinical testing The p.R12L variant (also known as c.35G>T), located in coding exon 1 of the FH gene, results from a G to T substitution at nucleotide position 35. The arginine at codon 12 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is not 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.
GeneDx RCV001771986 SCV001992940 uncertain significance not provided 2023-12-24 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Sema4, Sema4 RCV001020691 SCV002535559 uncertain significance Hereditary cancer-predisposing syndrome 2022-01-06 criteria provided, single submitter curation
Baylor Genetics RCV000700942 SCV004197354 uncertain significance Fumarase deficiency 2023-06-16 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001771986 SCV005625596 uncertain significance not provided 2024-08-22 criteria provided, single submitter clinical testing The FH c.35G>T (p.Arg12Leu) variant has not been reported in individuals with FH-related conditions in the published literature. The frequency of this variant in the general population, 0.00025 (4/15876 chromosomes in African/African American subpopulation (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is higher than would generally be expected for pathogenic variants in this gene. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Natera, Inc. RCV000700942 SCV001455900 uncertain significance Fumarase deficiency 2020-03-11 no assertion criteria provided clinical testing

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