Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001908956 | SCV002172660 | uncertain significance | not provided | 2021-12-13 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 1181 of the ELP1 protein (p.Lys1181Arg). This variant is present in population databases (rs367582146, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with ELP1-related conditions. 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 arginine 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. |
| Ambry Genetics | RCV003323946 | SCV002755812 | likely benign | not specified | 2021-11-24 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Fulgent Genetics, |
RCV002503546 | SCV002784802 | uncertain significance | Medulloblastoma; Familial dysautonomia | 2022-03-31 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003323946 | SCV004029827 | uncertain significance | not specified | 2023-07-27 | criteria provided, single submitter | clinical testing | Variant summary: ELP1 c.3542A>G (p.Lys1181Arg) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251464 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3542A>G in individuals affected with Familial Dysautonomia and no experimental evidence demonstrating its impact on protein function have been reported. Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as VUS and likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance. |