Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000256146 | SCV000321397 | uncertain significance | not provided | 2025-01-24 | criteria provided, single submitter | clinical testing | 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: 32956737, 37393059, 30043187) |
| Illumina Laboratory Services, |
RCV000327621 | SCV000452304 | uncertain significance | Pyridoxine-dependent epilepsy | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Labcorp Genetics |
RCV000327621 | SCV000640310 | likely benign | Pyridoxine-dependent epilepsy | 2025-01-15 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002392780 | SCV002697800 | uncertain significance | Inborn genetic diseases | 2018-07-19 | criteria provided, single submitter | clinical testing | The p.R469H variant (also known as c.1406G>A), located in coding exon 15 of the ALDH7A1 gene, results from a G to A substitution at nucleotide position 1406. The arginine at codon 469 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004782332 | SCV005395144 | uncertain significance | not specified | 2024-09-09 | criteria provided, single submitter | clinical testing | Variant summary: ALDH7A1 c.1406G>A (p.Arg469His) results in a non-conservative amino acid change located in the Aldehyde dehydrogenase domain (IPR015590) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00063 in 251198 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in ALDH7A1 causing Pyridoxine-Dependent Epilepsy (0.00063 vs 0.0018), allowing no conclusion about variant significance. c.1406G>A has been reported in the literature in a homozygous individual affected with Pyridoxine-Dependent Epilepsy (Coughlin_2019). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 30043187). ClinVar contains an entry for this variant (Variation ID: 265034). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| Centre de Biologie Pathologie Génétique, |
RCV001252144 | SCV001427894 | uncertain significance | Intellectual disability | 2019-01-01 | no assertion criteria provided | clinical testing |