Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000818997 | SCV000959636 | uncertain significance | Nemaline myopathy 9 | 2022-07-19 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 474 of the KLHL41 protein (p.Asp474Gly). This variant is present in population databases (rs145810515, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with KLHL41-related conditions. ClinVar contains an entry for this variant (Variation ID: 661557). 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 C15"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 | RCV002537439 | SCV003738935 | uncertain significance | Inborn genetic diseases | 2021-08-16 | criteria provided, single submitter | clinical testing | The c.1421A>G (p.D474G) alteration is located in exon 4 (coding exon 4) of the KLHL41 gene. This alteration results from a A to G substitution at nucleotide position 1421, causing the aspartic acid (D) at amino acid position 474 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |