Submissions for variant NM_000455.5(STK11):c.620A>G (p.Asp207Gly)

dbSNP: rs1555738370

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000632815	SCV000754010	uncertain significance	Peutz-Jeghers syndrome	2022-09-10	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with STK11-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 527820). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 207 of the STK11 protein (p.Asp207Gly).
Color Diagnostics, LLC DBA Color Health	RCV001175692	SCV001339399	uncertain significance	Hereditary cancer-predisposing syndrome	2023-08-17	criteria provided, single submitter	clinical testing	This missense variant replaces aspartic acid with glycine at codon 207 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.
GeneDx	RCV001766345	SCV001990038	uncertain significance	not provided	2019-05-22	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Genome-Nilou Lab	RCV000632815	SCV002057818	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000632815	SCV004816392	uncertain significance	Peutz-Jeghers syndrome	2023-09-17	criteria provided, single submitter	clinical testing	This missense variant replaces aspartic acid with glycine at codon 207 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.