ClinVar Miner

Submissions for variant NM_000143.3(FH):c.706A>G (p.Thr236Ala) (rs1064793126)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000482578 SCV000565004 likely pathogenic not provided 2015-03-30 criteria provided, single submitter clinical testing To our knowledge, the T236A variant, likely pathogenic in the FH gene has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. T236A is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/ function. Missense variants in nearby residues (L244R, H235R, R233H/L/C, L230R, I229T, and I228N) have been reported in the Human Gene Mutation Database in association with FH-related disorders (Stenson et al., 2009), supporting the functional importance of this region of the protein. Therefore, this variant is a strong candidate for a pathogenic variant; however, the possibility that it is a benign variant cannot be excluded.

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