Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Cancer Genomics Group, |
RCV001030706 | SCV001193628 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2019-05-01 | criteria provided, single submitter | research | |
Mendelics | RCV002249638 | SCV002518256 | uncertain significance | not specified | 2022-05-04 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002327243 | SCV002639668 | likely benign | Hereditary cancer-predisposing syndrome | 2022-08-02 | 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. |
Department of Pathology and Laboratory Medicine, |
RCV001357699 | SCV001553245 | uncertain significance | Lynch syndrome | no assertion criteria provided | clinical testing | The MSH2 p.Val150Phe variant was not identified in the literature nor was it identified in the dbSNP, ClinVar, or UMD-LSDB databases. The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016) or the Genome Aggregation Database (Feb 27, 2017). The p.Val150 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |