Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000467803 | SCV000541877 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2025-02-02 | 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 1039 of the ALK protein (p.Val1039Met). This variant is present in population databases (rs200080181, 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: 404367). 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. |
| St. |
RCV000761097 | SCV000891012 | uncertain significance | Familial isolated pituitary adenoma | 2021-05-20 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000467803 | SCV001302252 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2017-04-28 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
| Gene |
RCV002284391 | SCV002574657 | uncertain significance | not provided | 2022-09-14 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Present in cancer-free control individuals but not observed in melanoma cases (Pritchard et al., 2018); This variant is associated with the following publications: (PMID: 29641532) |
| Baylor Genetics | RCV000467803 | SCV004191683 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2024-03-21 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004948304 | SCV005591197 | likely benign | Hereditary cancer-predisposing syndrome | 2024-06-25 | 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. |