ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.1286C>G (p.Ala429Gly) (rs757369900)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000197676 SCV000254547 uncertain significance Peutz-Jeghers syndrome 2018-11-19 criteria provided, single submitter clinical testing This sequence change replaces alanine with glycine at codon 429 of the STK11 protein (p.Ala429Gly). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and glycine. While this variant is not present in population databases (rs757369900), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in an individual with an STK11-related disease. ClinVar contains an entry for this variant (Variation ID: 216428). 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, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000760078 SCV000565601 uncertain significance not provided 2016-03-29 criteria provided, single submitter clinical testing This variant is denoted STK11 c.1286C>G at the cDNA level, p.Ala429Gly (A429G) at the protein level, and results in the change of an Alanine to a Glycine (GCC>GGC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. STK11 Ala429Gly was not observed in approximately 5100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Alanine and Glycine share similar properties, this is considered a conservative amino acid substitution. STK11 Ala429Gly occurs at a position that is conserved in mammals and is not located in a known functional domain (UniProt). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether STK11 Ala429Gly is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000574953 SCV000672336 uncertain significance Hereditary cancer-predisposing syndrome 2017-02-28 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
Color RCV000574953 SCV000686619 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-09 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000760078 SCV000889852 uncertain significance not provided 2018-08-13 criteria provided, single submitter clinical testing

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