ClinVar Miner

Submissions for variant NM_000143.3(FH):c.1146G>A (p.Met382Ile) (rs863224006)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000198172 SCV000251480 likely pathogenic not provided 2017-10-02 criteria provided, single submitter clinical testing The M382I variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The variant is not observed in large population cohorts (Lek et al., 2016). M382I is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species; additionally, the Alanine 382 residue is located in a core helix involved in interation with two other monomers (Picaud et al., 2011). In silico analysis predicts this variant is probably damaging to the protein structure/function. Another missense variant in this residue (M382V) and nearby residues (N373S, N373D, Q376P, A385D, Q386R) have been reported in association with FH-related disorders, supporting the functional importance of this region of the protein. In summary, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded

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