Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000819660 | SCV000960333 | uncertain significance | Nemaline myopathy 8 | 2022-08-16 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 662094). This variant has not been reported in the literature in individuals affected with KLHL40-related conditions. This variant is present in population databases (rs759757085, gnomAD 0.008%). This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 415 of the KLHL40 protein (p.Tyr415His). |
Gene |
RCV002307629 | SCV002601035 | uncertain significance | not provided | 2022-05-13 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV003279109 | SCV003982257 | uncertain significance | Inborn genetic diseases | 2023-05-23 | criteria provided, single submitter | clinical testing | The c.1243T>C (p.Y415H) alteration is located in exon 2 (coding exon 2) of the KLHL40 gene. This alteration results from a T to C substitution at nucleotide position 1243, causing the tyrosine (Y) at amino acid position 415 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |