Submissions for variant NM_000474.4(TWIST1):c.277A>G (p.Ser93Gly)

gnomAD frequency: 0.00039  dbSNP: rs925811677

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002570785	SCV003683354	uncertain significance	Inborn genetic diseases	2021-07-08	criteria provided, single submitter	clinical testing	The c.277A>G (p.S93G) alteration is located in exon 1 (coding exon 1) of the TWIST1 gene. This alteration results from a A to G substitution at nucleotide position 277, causing the serine (S) at amino acid position 93 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003771743	SCV004577907	uncertain significance	TWIST1-related craniosynostosis; Saethre-Chotzen syndrome	2023-12-11	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 93 of the TWIST1 protein (p.Ser93Gly). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with TWIST1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1205866). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Not Available"; Align-GVGD: "Not Available". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Breakthrough Genomics, Breakthrough Genomics	RCV001572689	SCV005224575	likely benign	not provided		criteria provided, single submitter	not provided
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001572689	SCV001797440	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001572689	SCV001808745	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001572689	SCV001976110	likely benign	not provided		no assertion criteria provided	clinical testing