Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000685217 | SCV001330927 | uncertain significance | Familial dysautonomia | 2018-01-13 | 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 |
RCV001324208 | SCV001515152 | uncertain significance | not provided | 2021-12-18 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1306 of the ELP1 protein (p.Ser1306Leu). This variant is present in population databases (rs780649768, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ELP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 565613). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| Fulgent Genetics, |
RCV002493136 | SCV002791081 | uncertain significance | Medulloblastoma; Familial dysautonomia | 2022-03-19 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004026186 | SCV005021047 | uncertain significance | not specified | 2023-10-23 | criteria provided, single submitter | clinical testing | The p.S1306L variant (also known as c.3917C>T), located in coding exon 35 of the IKBKAP gene, results from a C to T substitution at nucleotide position 3917. The serine at codon 1306 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is conserved. 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. |
| Natera, |
RCV000685217 | SCV001452811 | uncertain significance | Familial dysautonomia | 2020-09-16 | no assertion criteria provided | clinical testing |