Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000667012 | SCV000791398 | uncertain significance | ALG6-congenital disorder of glycosylation 1C | 2017-05-09 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000667012 | SCV001588920 | pathogenic | ALG6-congenital disorder of glycosylation 1C | 2023-11-17 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 113 of the ALG6 protein (p.Arg113His). This variant is present in population databases (rs768372697, gnomAD 0.02%). This missense change has been observed in individual(s) with congenital disorder of glycosylation type 1c (PMID: 16321363). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 551854). 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 expected to disrupt ALG6 protein function with a positive predictive value of 80%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on ALG6 function (PMID: 16321363). This variant disrupts the p.Arg113 amino acid residue in ALG6. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 31117816). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002298726 | SCV002598875 | uncertain significance | not specified | 2022-09-08 | criteria provided, single submitter | clinical testing | Variant summary: ALG6 c.338G>A (p.Arg113His) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 250898 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.338G>A has been reported in the literature as a bialelic compound heterozygous genotype in at-least one individual affected with clinically and biochemically diagnosed Congenital Disorder Of Glycosylation Type 1C (Eklund_2006). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 classifying it as pathogenic (n=1) and VUS (n=1).Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| Baylor Genetics | RCV000667012 | SCV004197199 | likely pathogenic | ALG6-congenital disorder of glycosylation 1C | 2023-07-24 | criteria provided, single submitter | clinical testing |