NM_000455.4(STK11):c.1150C>T (p.Arg384Trp) AND Peutz-Jeghers syndrome

Clinical significance:Uncertain significance (Last evaluated: Aug 24, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000231028.7

Allele description [Variation Report for NM_000455.4(STK11):c.1150C>T (p.Arg384Trp)]

NM_000455.4(STK11):c.1150C>T (p.Arg384Trp)

Gene:
STK11:serine/threonine kinase 11 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19p13.3
Genomic location:
Preferred name:
NM_000455.4(STK11):c.1150C>T (p.Arg384Trp)
HGVS:
  • NC_000019.10:g.1226495C>T
  • NG_007460.2:g.42089C>T
  • NM_000455.4:c.1150C>T
  • NP_000446.1:p.Arg384Trp
  • LRG_319t1:c.1150C>T
  • LRG_319:g.42089C>T
  • LRG_319p1:p.Arg384Trp
  • NC_000019.9:g.1226494C>T
Protein change:
R384W
Links:
dbSNP: rs752015385
NCBI 1000 Genomes Browser:
rs752015385
Molecular consequence:
  • NM_000455.4:c.1150C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Peutz-Jeghers syndrome (PJS)
Synonyms:
Polyposis, hamartomatous intestinal; Polyps-and-spots syndrome; Peutz-Jeghers polyposis; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008280; MeSH: D010580; MedGen: C0031269; Orphanet: 2869; OMIM: 175200

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000284845Invitaecriteria provided, single submitter
Uncertain significance
(Aug 24, 2020)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV000785241Counsylcriteria provided, single submitter
Uncertain significance
(Jun 13, 2017)
unknownclinical testing

Counsyl_Autosomal_Dominant_Disease_Classification_criteria_(2015)_v1.pdf

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000284845.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces arginine with tryptophan at codon 384 of the STK11 protein (p.Arg384Trp). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs752015385, ExAC 0.004%). This variant has not been reported in the literature in individuals with STK11-related disease. ClinVar contains an entry for this variant (Variation ID: 234419). 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 tryptophan 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Counsyl, SCV000785241.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Aug 11, 2021

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