Submissions for variant NM_000455.5(STK11):c.427G>A (p.Val143Met)

gnomAD frequency: 0.00001  dbSNP: rs779987540

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000545253	SCV000629112	likely benign	Peutz-Jeghers syndrome	2025-01-21	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000579569	SCV000686644	uncertain significance	Hereditary cancer-predisposing syndrome	2022-08-29	criteria provided, single submitter	clinical testing	This missense variant replaces valine with methionine at codon 143 of the STK11 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 4/226056 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.
Ambry Genetics	RCV000579569	SCV001183912	uncertain significance	Hereditary cancer-predisposing syndrome	2023-06-23	criteria provided, single submitter	clinical testing	The p.V143M variant (also known as c.427G>A), located in coding exon 3 of the STK11 gene, results from a G to A substitution at nucleotide position 427. The valine at codon 143 is replaced by methionine, an amino acid with highly similar properties. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001269189	SCV001448476	uncertain significance	not specified	2020-11-25	criteria provided, single submitter	clinical testing	Variant summary: STK11 c.427G>A (p.Val143Met) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.8e-05 in 226056 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, c.427G>A, has not been reported in the literature in individuals affected with Peutz-Jeghers Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Genome-Nilou Lab	RCV000545253	SCV002057787	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
GeneDx	RCV001836837	SCV002097453	uncertain significance	not provided	2023-04-19	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 15863673, 27300552, 29973652)
Sema4, Sema4	RCV000579569	SCV002531694	uncertain significance	Hereditary cancer-predisposing syndrome	2021-12-27	criteria provided, single submitter	curation
All of Us Research Program, National Institutes of Health	RCV000545253	SCV004816354	uncertain significance	Peutz-Jeghers syndrome	2024-08-06	criteria provided, single submitter	clinical testing	This missense variant replaces valine with methionine at codon 143 of the STK11 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 4/226056 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.