Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000459873 | SCV000541856 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2024-12-02 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 806 of the ALK protein (p.Arg806Cys). This variant is present in population databases (rs80227749, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ALK-related conditions. ClinVar contains an entry for this variant (Variation ID: 404347). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 |
RCV003409611 | SCV004113215 | uncertain significance | ALK-related disorder | 2022-09-14 | criteria provided, single submitter | clinical testing | The ALK c.2416C>T variant is predicted to result in the amino acid substitution p.Arg806Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.020% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-29456502-G-A) and is interpreted as uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/404347/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| Baylor Genetics | RCV000459873 | SCV004198094 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2024-02-06 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV004722761 | SCV005333110 | uncertain significance | not provided | 2024-01-17 | criteria provided, single submitter | clinical testing | 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 | RCV004948300 | SCV005590380 | benign | Hereditary cancer-predisposing syndrome | 2024-08-20 | criteria provided, single submitter | clinical testing | This alteration is classified as 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. |