Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000186732 | SCV000240299 | uncertain significance | not provided | 2013-09-06 | criteria provided, single submitter | clinical testing | p.Tyr69Cys (TAT>TGT): c.206 A>G in exon 2 of the ALDH7A1 gene (NM_001182.3). The Tyr69Cys missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Although both Tyrosine and Cysteine are uncharged, polar amino acid residues, the gain of a Cysteine may affect the formation of disulfide bonds in the protein. Tyr69Cys alters a highly conserved position in the NAD-binding domain of the ALDH7A1 protein. However, in silico analysis is inconsistent with regard to the effect this variant may have on the protein structure/function. Therefore, based on the currently available information, it is unclear whether Tyr69Cys is a disease-causing mutation or a rare benign variant. The variant is found in INFANT-EPI panel(s). |
Invitae | RCV001372096 | SCV001568691 | uncertain significance | Pyridoxine-dependent epilepsy | 2020-05-20 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with ALDH7A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 204836). This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with cysteine at codon 69 of the ALDH7A1 protein (p.Tyr69Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine. |
Genome- |
RCV001372096 | SCV004050343 | uncertain significance | Pyridoxine-dependent epilepsy | 2023-04-11 | criteria provided, single submitter | clinical testing |