Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000570526 | SCV000664349 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-04-22 | criteria provided, single submitter | clinical testing | The p.M18I variant (also known as c.54G>A), located in coding exon 1 of the STK11 gene, results from a G to A substitution at nucleotide position 54. The methionine at codon 18 is replaced by isoleucine, an amino acid with highly similar properties. This alteration was seen in 0/732 breast cancer patients, 0/189 colorectal cancer patients and 1/490 cancer-free elderly controls in a Turkish population (Akcay IM et al. Int J Cancer, 2021 01;148:285-295). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Color Diagnostics, |
RCV000570526 | SCV000904231 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-02-21 | criteria provided, single submitter | clinical testing | This missense variant replaces methionine with isoleucine at codon 18 of the STK11 protein. Computational prediction suggests that this variant may not impact protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with STK11-related disorders in the literature. This variant has been identified in 1/241242 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Labcorp Genetics |
RCV001219409 | SCV001391345 | uncertain significance | Peutz-Jeghers syndrome | 2024-04-29 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 18 of the STK11 protein (p.Met18Ile). This variant is present in population databases (rs755436889, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with STK11-related conditions. ClinVar contains an entry for this variant (Variation ID: 480711). 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 with a negative predictive value of 95%. 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. |
Genome- |
RCV001219409 | SCV002057724 | uncertain significance | Peutz-Jeghers syndrome | 2021-07-15 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV004569134 | SCV005052864 | uncertain significance | Melanoma, cutaneous malignant, susceptibility to, 1 | 2024-03-22 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV001219409 | SCV005425387 | uncertain significance | Peutz-Jeghers syndrome | 2024-03-24 | criteria provided, single submitter | clinical testing | This missense variant replaces methionine with isoleucine at codon 18 of the STK11 protein. Computational prediction suggests that this variant may not impact protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with STK11-related disorders in the literature. This variant has been identified in 1/241242 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Department of Pathology and Laboratory Medicine, |
RCV005398884 | SCV006054149 | uncertain significance | Peutz-Jeghers syndrome; Melanoma, cutaneous malignant, susceptibility to, 1; Familial pancreatic carcinoma; Germ cell tumor of testis | 2024-10-28 | criteria provided, single submitter | clinical testing |