Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003556159 | SCV004294996 | likely pathogenic | not provided | 2024-01-19 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 626 of the STT3A protein (p.Val626Ala). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with congenital disorder of glycosylation (PMID: 23842455, 28424003). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 102443). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt STT3A protein function with a negative predictive value of 80%. Studies have shown that this missense change alters STT3A gene expression (PMID: 23842455). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
OMIM | RCV000088679 | SCV000121601 | pathogenic | STT3A-congenital disorder of glycosylation | 2013-11-15 | no assertion criteria provided | literature only |