Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001472415 | SCV001676547 | pathogenic | TWIST1-related craniosynostosis; Saethre-Chotzen syndrome | 2022-06-07 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 159 of the TWIST1 protein (p.Leu159Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with craniosynostosis and/or Saethre-Chotzen syndrome (PMID: 10094188; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 572211). 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"). Experimental studies have shown that this missense change affects TWIST1 function (PMID: 10749989). For these reasons, this variant has been classified as Pathogenic. |