ClinVar Miner

Submissions for variant NM_000474.4(TWIST1):c.132_142del (p.Ser45fs) (rs1554442082)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000653735 SCV000775625 pathogenic Craniosynostosis 1; Saethre-Chotzen syndrome 2017-08-24 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the TWIST1 gene (p.Ser45Argfs*189). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 158 amino acids of the TWIST1 protein. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported in an individual with Saethre-Chotzen syndrome-like features (PMID: 14513358). This variant is also known as 128_138del11 in the literature. A different frameshift downstream of this variant (p.Thr137Hisfs*101) has been determined to be likely pathogenic (PMID: 24127277, Invitae). This suggests that disruptions of this region of the TWIST1 protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.

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