Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000786069 | SCV002250311 | uncertain significance | Congenital myasthenic syndrome 12 | 2021-07-28 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 617540). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. This variant has not been reported in the literature in individuals affected with GFPT1-related conditions. This sequence change replaces arginine with glutamine at codon 17 of the GFPT1 protein (p.Arg17Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs775399768, ExAC 0.002%). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002265872 | SCV002548168 | uncertain significance | not specified | 2022-05-24 | criteria provided, single submitter | clinical testing | Variant summary: GFPT1 c.50G>A (p.Arg17Gln) results in a conservative amino acid change located in the Glutamine amidotransferase type 2 domain (IPR017932) of the encoded protein sequence. Four 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 251264 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.50G>A has been reported in the literature as a presumed compound heterozygous genotype in at-least one individual affected with Congenital Myasthenic Syndrome who underwent clinical exome sequencing (example, Borklu-Yucel_2020). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory representing the published report cited above classified the variant as likely pathogenic and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Genetic Diseases Diagnostic Center, |
RCV000786069 | SCV000864401 | likely pathogenic | Congenital myasthenic syndrome 12 | 2018-12-18 | no assertion criteria provided | clinical testing |