ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.1189G>T (p.Ala397Ser) (rs587780008)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115595 SCV000149504 uncertain significance not provided 2016-10-25 criteria provided, single submitter clinical testing This variant is denoted STK11 c.1189G>T at the cDNA level, p.Ala397Ser (A397S) at the protein level, and results in the change of an Alanine to a Serine (GCG>TCG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. STK11 Ala397Ser was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Alanine and Serine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. STK11 Ala397Ser occurs at a position that is not conserved and is located in the C-terminal domain (Hearle 2006). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether STK11 Ala397Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000195603 SCV000254543 uncertain significance Peutz-Jeghers syndrome 2018-09-04 criteria provided, single submitter clinical testing This sequence change replaces alanine with serine at codon 397 of the STK11 protein (p.Ala397Ser). The alanine residue is weakly conserved and there is a moderate physicochemical difference between alanine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with colorectal cancer (PMID: 28135145). ClinVar contains an entry for this variant (Variation ID: 127699). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Ambry Genetics RCV000576049 SCV000664347 likely benign Hereditary cancer-predisposing syndrome 2016-10-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Other data supporting benign classification
Color RCV000576049 SCV000911367 likely benign Hereditary cancer-predisposing syndrome 2015-07-15 criteria provided, single submitter clinical testing

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