Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV003441701 | SCV004168789 | likely pathogenic | not provided | 2023-04-20 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31589614, 10094194, 30916489, 21729033, 28236338, 12915478, 36980989, 25766764) |
Invitae | RCV003441701 | SCV004293942 | pathogenic | not provided | 2023-10-17 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1651 of the ABCA12 protein (p.Gly1651Ser). This variant is present in population databases (rs28940568, gnomAD 0.007%). This missense change has been observed in individual(s) with lamellar ichthyosis (PMID: 12915478, 21729033). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 2856). 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 ABCA12 protein function. For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000002990 | SCV000023148 | pathogenic | Autosomal recessive congenital ichthyosis 4A | 2003-09-15 | no assertion criteria provided | literature only | |
Center for Genomic Medicine, |
RCV003988819 | SCV004805552 | uncertain significance | Autosomal recessive congenital ichthyosis 4B | 2024-03-25 | flagged submission | research |