Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000460323 | SCV000550049 | uncertain significance | Gastrointestinal stromal tumor | 2025-01-14 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 974 of the KIT protein (p.Asp974Asn). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with KIT-related conditions. ClinVar contains an entry for this variant (Variation ID: 409715). 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 tolerated. 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. |
| Sema4, |
RCV002258913 | SCV002536400 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-05-02 | criteria provided, single submitter | curation | |
| Ambry Genetics | RCV002258913 | SCV002746019 | benign | Hereditary cancer-predisposing syndrome | 2024-07-08 | 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. |
| Gene |
RCV003313073 | SCV004012375 | uncertain significance | not provided | 2024-02-23 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| St. |
RCV000460323 | SCV004171401 | uncertain significance | Gastrointestinal stromal tumor | 2023-11-13 | criteria provided, single submitter | clinical testing | The KIT c.2920G>A (p.Asp974Asn) missense change has a maximum subpopulation frequency of 0.05% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been reported in individuals with KIT-related gastrointestinal stromal tumor. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |
| Baylor Genetics | RCV000460323 | SCV004190379 | uncertain significance | Gastrointestinal stromal tumor | 2024-01-20 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV005027519 | SCV005658226 | uncertain significance | Gastrointestinal stromal tumor; Piebaldism; Acute myeloid leukemia; Cutaneous mastocytosis; Germ cell tumor of testis | 2024-05-05 | criteria provided, single submitter | clinical testing |