ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.580G>A (p.Asp194Asn) (rs121913315)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000168375 SCV000219066 pathogenic Peutz-Jeghers syndrome 2019-08-30 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 194 of the STK11 protein (p.Asp194Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in several individuals and families affected with Peutz-Jeghers syndrome (PJS) (PMID: 10408777, 23718779, 16582077, 12865922, 25226294, 17026623, 20435009, 16287113) and colorectal polyposis (PMID: 23399955). This variant was also reported to segregate with PJS in a family (PMID: 10408777). ClinVar contains an entry for this variant (Variation ID: 188348). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This sequence change falls in a mutational 'hotspot', which is defined as a clustering of plausible observations within a localized region of the protein (PMID: 19892943, 14976552, 14517248, 21189378, 23240097). This indicates that this region of the protein may be critical for proper protein function. For these reasons, this variant has been classified as Pathogenic.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000708629 SCV000331163 pathogenic not provided 2015-09-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV000492479 SCV000580886 likely pathogenic Hereditary cancer-predisposing syndrome 2019-09-23 criteria provided, single submitter clinical testing Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
GeneKor MSA RCV000708629 SCV000821781 likely pathogenic not provided 2020-01-01 criteria provided, single submitter clinical testing This variant is a substitution of aspartic acid with asparagine at position 194 of the STK11 protein. This particular aspartic acid is highly conserved and there is small physicochemical variation caused by the change. The mutation is absent from population databases but it is reported in literature in individual or families affected by colorectal cancer and the Peutz-Jeghers syndrome (PMID:23399955, PMID: 10408777, PMID: 16582077). The mutation is located in a region of the protein that is considered to be particularly important for its proper function thus the mutation frequency in this region is high, thus it is considered a mutational 'hotspot' region (PMID: 14976552, PMID:14517248, PMID:21189378, PMID:23240097). The mutation database ClinVar contains entries for this variant (Variation ID: 188348).
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000708629 SCV001134844 pathogenic not provided 2019-04-15 criteria provided, single submitter clinical testing Not found in the total gnomAD dataset, and the data is high quality (0/252614 chr). Statistically enriched in patients compared to ethnically matched controls. Predicted to have a damaging effect on the protein. Two other pathogenic or likely pathogenic variants affect the same amino acid. One de novo case with parental identity confirmed.
Color RCV000492479 SCV001340646 likely pathogenic Hereditary cancer-predisposing syndrome 2018-12-20 criteria provided, single submitter clinical testing
Database of Curated Mutations (DoCM) RCV000445048 SCV000505689 likely pathogenic Neoplasm 2015-07-14 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427095 SCV000505690 likely pathogenic Lung adenocarcinoma 2016-05-13 no assertion criteria provided literature only

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