Submissions for variant NM_000455.5(STK11):c.248A>G (p.Lys83Arg)

dbSNP: rs374006397

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000217408	SCV000279527	uncertain significance	not provided	2022-06-07	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)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000539793	SCV000629100	likely benign	Peutz-Jeghers syndrome	2024-09-27	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000565378	SCV000675256	uncertain significance	Hereditary cancer-predisposing syndrome	2024-08-28	criteria provided, single submitter	clinical testing	The p.K83R variant (also known as c.248A>G), located in coding exon 1 of the STK11 gene, results from an A to G substitution at nucleotide position 248. The lysine at codon 83 is replaced by arginine, 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. Based on the available evidence, the clinical significance of this variant remains unclear.
Color Diagnostics, LLC DBA Color Health	RCV000565378	SCV000686625	uncertain significance	Hereditary cancer-predisposing syndrome	2023-11-16	criteria provided, single submitter	clinical testing	This missense variant replaces lysine with arginine at codon 83 of the STK11 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). 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 1/242186 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.
Genome-Nilou Lab	RCV000539793	SCV002057756	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000565378	SCV002531677	uncertain significance	Hereditary cancer-predisposing syndrome	2021-06-12	criteria provided, single submitter	curation
All of Us Research Program, National Institutes of Health	RCV000539793	SCV004816330	uncertain significance	Peutz-Jeghers syndrome	2023-12-13	criteria provided, single submitter	clinical testing	This missense variant replaces lysine with arginine at codon 83 of the STK11 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). 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 1/242186 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.
Fulgent Genetics, Fulgent Genetics	RCV005025369	SCV005655478	uncertain significance	Peutz-Jeghers syndrome; Melanoma, cutaneous malignant, susceptibility to, 1; Familial pancreatic carcinoma; Germ cell tumor of testis	2024-02-14	criteria provided, single submitter	clinical testing