Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002318000 | SCV000849577 | uncertain significance | Inborn genetic diseases | 2017-05-31 | criteria provided, single submitter | clinical testing | The p.F204L variant (also known as c.612T>G), located in coding exon 1 of the NHLRC1 gene, results from a T to G substitution at nucleotide position 612. The phenylalanine at codon 204 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and leucine is the reference amino acid in other vertebrate species. 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. |
Invitae | RCV001214315 | SCV001385990 | uncertain significance | Lafora disease | 2022-06-13 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 204 of the NHLRC1 protein (p.Phe204Leu). This variant is present in population databases (rs201058506, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with NHLRC1-related conditions. ClinVar contains an entry for this variant (Variation ID: 589056). 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. |
Gene |
RCV001766578 | SCV001991865 | uncertain significance | not provided | 2019-04-08 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |