ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.1225C>G (p.Arg409Gly) (rs368466538)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132082 SCV000187146 uncertain significance Hereditary cancer-predisposing syndrome 2016-09-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000132082 SCV000691480 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-23 criteria provided, single submitter clinical testing
Counsyl RCV000409343 SCV000489274 uncertain significance Peutz-Jeghers syndrome 2016-09-12 criteria provided, single submitter clinical testing
GeneDx RCV000509169 SCV000211727 uncertain significance not provided 2016-05-04 criteria provided, single submitter clinical testing This variant is denoted STK11 c.1225C>G at the cDNA level, p.Arg409Gly (R409G) at the protein level, and results in the change of an Arginine to a Glycine (CGG>GGG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. STK11 Arg409Gly was not observed in approximately 6,500 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 Arginine and Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. STK11 Arg409Gly occurs at a position that is not conserved across species 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 information, it is unclear whether STK11 Arg409Gly is pathogenic or benign. We consider it to be a variant of uncertain significance.
GenomeConnect, ClinGen RCV000509169 SCV000606988 not provided not provided no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Invitae RCV000409343 SCV000629078 uncertain significance Peutz-Jeghers syndrome 2018-03-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 409 of the STK11 protein (p.Arg409Gly). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with STK11-related disease. ClinVar contains an entry for this variant (Variation ID: 142713). 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, 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.

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