Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003095695 | SCV003486929 | uncertain significance | ALG12-congenital disorder of glycosylation | 2024-01-19 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 157 of the ALG12 protein (p.Val157Leu). This variant also falls at the last nucleotide of exon 4, which is part of the consensus splice site for this exon. This variant is present in population databases (rs144851629, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with ALG12-related conditions. ClinVar contains an entry for this variant (Variation ID: 2171186). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
| Greenwood Genetic Center Diagnostic Laboratories, |
RCV003387545 | SCV004099101 | uncertain significance | not provided | 2023-09-05 | criteria provided, single submitter | clinical testing | PM2, PP3 |