Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000303490 | SCV000360209 | uncertain significance | Junctional epidermolysis bullosa, non-Herlitz type | 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. |
| Fulgent Genetics, |
RCV002504049 | SCV002814647 | uncertain significance | Epithelial recurrent erosion dystrophy; Epidermolysis bullosa, junctional 4, intermediate | 2022-03-23 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002520535 | SCV003283455 | uncertain significance | not provided | 2022-09-19 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1361 of the COL17A1 protein (p.Gly1361Arg). This variant is present in population databases (rs143021968, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with COL17A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 298688). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a 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. |
| Ambry Genetics | RCV002520534 | SCV003715920 | uncertain significance | Inborn genetic diseases | 2021-09-16 | criteria provided, single submitter | clinical testing | The c.4081G>A (p.G1361R) alteration is located in exon 52 (coding exon 51) of the COL17A1 gene. This alteration results from a G to A substitution at nucleotide position 4081, causing the glycine (G) at amino acid position 1361 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |