Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Pediatric Genomic Medicine, |
RCV000224157 | SCV000280802 | uncertain significance | not provided | 2015-06-05 | criteria provided, single submitter | clinical testing | Converted during submission to Uncertain significance. |
Labcorp Genetics |
RCV001219590 | SCV001391536 | uncertain significance | Familial hemophagocytic lymphohistiocytosis 3 | 2022-07-17 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 91 of the UNC13D protein (p.Val91Met). This variant is present in population databases (rs374308904, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with UNC13D-related conditions. ClinVar contains an entry for this variant (Variation ID: 235323). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The methionine 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. |
Prevention |
RCV003422127 | SCV004118152 | uncertain significance | UNC13D-related disorder | 2023-01-04 | criteria provided, single submitter | clinical testing | The UNC13D c.271G>A variant is predicted to result in the amino acid substitution p.Val91Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.010% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-73839145-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Ambry Genetics | RCV004020718 | SCV004975432 | likely benign | Inborn genetic diseases | 2023-02-23 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |