ClinVar Miner

Submissions for variant NM_000143.4(FH):c.67G>A (p.Ala23Thr)

dbSNP: rs1573889943
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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 RCV001025670 SCV001187908 uncertain significance Hereditary cancer-predisposing syndrome 2019-09-23 criteria provided, single submitter clinical testing The p.A23T variant (also known as c.67G>A), located in coding exon 1 of the FH gene, results from a G to A substitution at nucleotide position 67. The alanine at codon 23 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved on limited sequence alignment. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV002551934 SCV002119595 uncertain significance not provided 2024-01-07 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 23 of the FH protein (p.Ala23Thr). This variant is not present in population databases (gnomAD no frequency). 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: 826631). 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 with a negative predictive value of 95%. 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. RCV001827208 SCV002085904 uncertain significance Fumarase deficiency 2021-05-26 no assertion criteria provided clinical testing

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