Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000536736 | SCV000629074 | uncertain significance | Peutz-Jeghers syndrome | 2023-09-10 | criteria provided, single submitter | clinical testing | 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 not expected to disrupt STK11 protein function. ClinVar contains an entry for this variant (Variation ID: 458020). This missense change has been observed in individual(s) with rectal cancer (PMID: 28135145). 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 sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 394 of the STK11 protein (p.Gly394Arg). |
Ambry Genetics | RCV000565643 | SCV000672343 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-06-03 | criteria provided, single submitter | clinical testing | The p.G394R variant (also known as c.1180G>C), located in coding exon 9 of the STK11 gene, results from a G to C substitution at nucleotide position 1180. The glycine at codon 394 is replaced by arginine, an amino acid with dissimilar properties. This variant has been reported in an individual affected with MSS colorectal cancer at age 29; however, this individual also was found to be heterozygous for an MSH6 pathogenic mutation (Yurgelun MB et al. J. Clin. Oncol., 2017 Apr;35:1086-1095). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Color Diagnostics, |
RCV000565643 | SCV001351987 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-03-19 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV000536736 | SCV002057959 | uncertain significance | Peutz-Jeghers syndrome | 2021-07-15 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV004568744 | SCV005052892 | uncertain significance | Melanoma, cutaneous malignant, susceptibility to, 1 | 2023-11-08 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV000536736 | SCV005425441 | uncertain significance | Peutz-Jeghers syndrome | 2024-09-23 | criteria provided, single submitter | clinical testing |