Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV003164591 | SCV003858824 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-01-19 | criteria provided, single submitter | clinical testing | The p.Q364* pathogenic mutation (also known as c.1090C>T), located in coding exon 8 of the STK11 gene, results from a C to T substitution at nucleotide position 1090. This changes the amino acid from a glutamine to a stop codon within coding exon 8. This alteration was observed with an allele frequency of 0 in 7,051 unselected female breast cancer patients and was observed with an allele frequency of 0.00009 in 11,241 female controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 Oct;9:4083). This variant was present in 0/1005 Japanese pancreatic cancer patients and at a carrier frequency of 0.00004 in 23705 controls (Mizukami K et al. EBioMedicine, 2020 Oct;60:103033). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003235727 | SCV003934520 | pathogenic | Peutz-Jeghers syndrome | 2023-05-22 | criteria provided, single submitter | clinical testing | Variant summary: STK11 c.1090C>T (p.Gln364X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein, which is a commonly known mechanism for disease. While this variant is not expected to result in nonsense mediated decay, it is predicted to disrupt the last 70 amino acids of the protein. At least one downstream truncating variant, c.1246A>T (p.K416X), has been reported in the literature in a patient with Peutz-Jeghers syndrome (PMID: 10353780). The variant allele was found at a frequency of 3.7e-06 in 268031 control chromosomes (i.e., 1 heterozygous carrier; gnomAD and Mizukami_2020). 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.1090C>T in individuals affected with Peutz-Jeghers Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. The following publications have been ascertained in the context of this evaluation (PMID: 32980694, 30287823). Two ClinVar submitters (evaluation after 2014) have cited the variant, and both submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Invitae | RCV003235727 | SCV004551775 | pathogenic | Peutz-Jeghers syndrome | 2023-11-17 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln364*) in the STK11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in STK11 are known to be pathogenic (PMID: 15188174, 16287113). This variant is not present in population databases (gnomAD no frequency). 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: 1801558). For these reasons, this variant has been classified as Pathogenic. |
| Laboratory for Genotyping Development, |
RCV003164592 | SCV002758238 | pathogenic | Gastric cancer | 2021-07-01 | no assertion criteria provided | research |