Submissions for variant NM_000455.5(STK11):c.617C>T (p.Ala206Val)

dbSNP: rs764244639

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000163146	SCV000213663	likely benign	Hereditary cancer-predisposing syndrome	2019-07-09	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Counsyl	RCV000412198	SCV000488269	uncertain significance	Peutz-Jeghers syndrome	2016-02-10	criteria provided, single submitter	clinical testing
GeneDx	RCV000478878	SCV000566068	uncertain significance	not provided	2021-09-22	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with breast cancer (Stuttgen 2019); This variant is associated with the following publications: (PMID: 28199989, 30287823, 15863673, 31465090)
Invitae	RCV000412198	SCV000629133	uncertain significance	Peutz-Jeghers syndrome	2023-10-23	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 206 of the STK11 protein (p.Ala206Val). 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 missense change has been observed in individual(s) with breast cancer (PMID: 31465090). ClinVar contains an entry for this variant (Variation ID: 184032). 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. 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.
Color Diagnostics, LLC DBA Color Health	RCV000163146	SCV000911131	uncertain significance	Hereditary cancer-predisposing syndrome	2023-01-09	criteria provided, single submitter	clinical testing	This missense variant replaces alanine with valine at codon 206 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 not been identified 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.
Illumina Laboratory Services, Illumina	RCV000412198	SCV001284039	uncertain significance	Peutz-Jeghers syndrome	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Genome-Nilou Lab	RCV000412198	SCV002057269	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000478878	SCV002063698	uncertain significance	not provided	2021-12-01	criteria provided, single submitter	clinical testing
Mendelics	RCV002247563	SCV002519413	uncertain significance	not specified	2022-05-04	criteria provided, single submitter	clinical testing
MGZ Medical Genetics Center	RCV000412198	SCV002578971	uncertain significance	Peutz-Jeghers syndrome	2022-03-29	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000412198	SCV004017922	uncertain significance	Peutz-Jeghers syndrome	2023-04-12	criteria provided, single submitter	clinical testing	This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
All of Us Research Program, National Institutes of Health	RCV000412198	SCV004816389	uncertain significance	Peutz-Jeghers syndrome	2023-08-08	criteria provided, single submitter	clinical testing	This missense variant replaces alanine with valine at codon 206 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified 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.