Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000157950 | SCV000207885 | uncertain significance | not provided | 2020-05-18 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function; Benign missense variants in this gene are rare (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 28424201) |
| Illumina Laboratory Services, |
RCV000349904 | SCV000377748 | uncertain significance | Noonan syndrome | 2016-06-14 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001280675 | SCV001467971 | uncertain significance | not specified | 2020-12-21 | criteria provided, single submitter | clinical testing | Variant summary: KRAS c.389C>T (p.Ala130Val) results in a non-conservative amino acid change located in the Small GTP-binding protein domain (IPR005225) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 251168 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.389C>T in individuals affected with Noonan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Labcorp Genetics |
RCV001368828 | SCV001565242 | uncertain significance | RASopathy | 2023-07-18 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs730880473, gnomAD 0.004%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 130 of the KRAS protein (p.Ala130Val). This variant has not been reported in the literature in individuals affected with KRAS-related conditions. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KRAS protein function. ClinVar contains an entry for this variant (Variation ID: 180861). |
| Fulgent Genetics, |
RCV002478474 | SCV002789914 | uncertain significance | Familial cancer of breast; Noonan syndrome 3; Linear nevus sebaceous syndrome; Toriello-Lacassie-Droste syndrome; Cerebral arteriovenous malformation; Malignant tumor of urinary bladder; Carcinoma of pancreas; Autoimmune lymphoproliferative syndrome type 4; Acute myeloid leukemia; Cardiofaciocutaneous syndrome 2; Gastric cancer; Lung cancer | 2022-05-19 | criteria provided, single submitter | clinical testing |