ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.1148G>A (p.Arg383His) (rs730881990)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235216 SCV000211725 uncertain significance not provided 2017-08-07 criteria provided, single submitter clinical testing This variant is denoted STK11 c.1148G>A at the cDNA level, p.Arg383His (R383H) at the protein level, and results in the change of an Arginine to a Histidine (CGC>CAC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. STK11 Arg383His was not observed at a significant allele frequency in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Arginine and Histidine share similar properties, this is considered a conservative amino acid substitution. STK11 Arg383His occurs at a position that is not conserved and is located in the C-terminal domain (Hearle 2006). 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 Arg383His is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000161013 SCV000214142 uncertain significance Hereditary cancer-predisposing syndrome 2017-09-21 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000204343 SCV000259503 uncertain significance Peutz-Jeghers syndrome 2018-06-12 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 383 of the STK11 protein (p.Arg383His). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs730881990, ExAC 0.01%). This variant has not been reported in the literature in individuals with a STK11-related disease. ClinVar contains an entry for this variant (Variation ID: 182918). 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 and their clinical significance is uncertain. In summary, this variant has uncertain impact on STK11 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV000161013 SCV000686596 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-14 criteria provided, single submitter clinical testing
GeneKor MSA RCV000161013 SCV000822203 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing

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