ClinVar Miner

Submissions for variant NM_000474.4(TWIST1):c.476T>C (p.Leu159Pro) (rs1585616825)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000802611 SCV000942450 uncertain significance Craniosynostosis 1; Saethre-Chotzen syndrome 2019-04-02 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 159 of the TWIST1 protein (p.Leu159Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in a family affected with craniosynostosis (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Leu159 amino acid residue in TWIST1. Other variant(s) that disrupt this residue have been observed in individuals with TWIST1-related conditions (PMID: 10094188), which suggests that this may be a clinically significant amino acid residue. 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.

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