Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000632802 | SCV000753997 | likely benign | Peutz-Jeghers syndrome | 2023-10-05 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001017452 | SCV001178535 | likely benign | Hereditary cancer-predisposing syndrome | 2024-01-16 | 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. |
| Color Diagnostics, |
RCV001017452 | SCV001339398 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-03-14 | criteria provided, single submitter | clinical testing | |
| Genome- |
RCV000632802 | SCV002057942 | uncertain significance | Peutz-Jeghers syndrome | 2021-07-15 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV001355465 | SCV001550358 | uncertain significance | Familial ovarian cancer | no assertion criteria provided | clinical testing | The STK11 p.Gln382Arg variant was not identified in the literature nor was it identified in the LOVD-3.0 database. The variant was identified in dbSNP (ID: rs985937027) as “NA” and Clinvar (classified as uncertain significance by Invitae). The variant was identified in control databases in 1 of 30914 chromosomes at a frequency of 0.00003 (Genome Aggregation Database Feb 27, 2017); it was observed in the following European Non-Finnish population in 1 of 14982 chromosomes (freq: 0.00007), while it was not observed in the African, Other, Latino, Ashkenazi Jewish, East Asian, European Finnish, or South Asian populations. The p.Gln382 residue is conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood that the Arg variant impacts 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. |