ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.1243C>T (p.Arg415Cys) (rs864622448)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000469436 SCV000541167 uncertain significance Peutz-Jeghers syndrome 2018-11-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 415 of the STK11 protein (p.Arg415Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. While this variant is not present in population databases, 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 individuals with STK11-related disease. ClinVar contains an entry for this variant (Variation ID: 403796). 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 disruptive, 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.
GeneDx RCV000484937 SCV000567830 uncertain significance not provided 2017-11-27 criteria provided, single submitter clinical testing This variant is denoted STK11 c.1243C>T at the cDNA level, p.Arg415Cys (R415C) at the protein level, and results in the change of an Arginine to a Cysteine (CGC>TGC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. STK11 Arg415Cys was not observed in large population cohorts (Lek 2016). Since Arginine and Cysteine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. STK11 Arg415Cys is not located in a known functional domain. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure or function. Based on currently available evidence, it is unclear whether STK11 Arg415Cys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000570343 SCV000672315 uncertain significance Hereditary cancer-predisposing syndrome 2017-01-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000570343 SCV000686607 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-29 criteria provided, single submitter clinical testing
Counsyl RCV000469436 SCV000785620 uncertain significance Peutz-Jeghers syndrome 2017-10-16 criteria provided, single submitter clinical testing

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