Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001042182 | SCV001205849 | uncertain significance | not provided | 2022-10-28 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 177 of the CLRN1 protein (p.Val177Ile). This variant is present in population databases (rs753739519, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with CLRN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 840237). 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 isoleucine 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 |
RCV001042182 | SCV002588100 | uncertain significance | not provided | 2022-10-28 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV004973269 | SCV005559447 | uncertain significance | Inborn genetic diseases | 2024-09-08 | criteria provided, single submitter | clinical testing | The c.529G>A (p.V177I) alteration is located in exon 3 (coding exon 3) of the CLRN1 gene. This alteration results from a G to A substitution at nucleotide position 529, causing the valine (V) at amino acid position 177 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Natera, |
RCV001275851 | SCV001461429 | uncertain significance | Usher syndrome type 3A | 2020-05-02 | no assertion criteria provided | clinical testing |