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NM_005359.6(SMAD4):c.26C>T (p.Thr9Ile) AND Juvenile polyposis syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 23, 2017
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002231712.14

Allele description [Variation Report for NM_005359.6(SMAD4):c.26C>T (p.Thr9Ile)]

NM_005359.6(SMAD4):c.26C>T (p.Thr9Ile)

Gene:
SMAD4:SMAD family member 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
18q21.2
Genomic location:
Preferred name:
NM_005359.6(SMAD4):c.26C>T (p.Thr9Ile)
HGVS:
  • NC_000018.10:g.51047072C>T
  • NG_013013.2:g.84033C>T
  • NM_005359.6:c.26C>TMANE SELECT
  • NP_005350.1:p.Thr9Ile
  • NP_005350.1:p.Thr9Ile
  • LRG_318t1:c.26C>T
  • LRG_318:g.84033C>T
  • LRG_318p1:p.Thr9Ile
  • NC_000018.9:g.48573442C>T
  • NM_005359.5:c.26C>T
Protein change:
T9I
Links:
dbSNP: rs1555684986
NCBI 1000 Genomes Browser:
rs1555684986
Molecular consequence:
  • NM_005359.6:c.26C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Juvenile polyposis syndrome (JPS)
Synonyms:
Polyposis juvenile intestinal; Polyposis familial of entire gastrointestinal tract
Identifiers:
MONDO: MONDO:0017380; MedGen: C0345893; Orphanet: 2929; OMIM: 174900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000632780Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(May 23, 2017) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000632780.4

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

Description

This sequence change replaces threonine with isoleucine at codon 9 of the SMAD4 protein (p.Thr9Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. In summary, this variant has uncertain impact on SMAD4 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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. This variant has not been reported in the literature in individuals with a SMAD4-related disease. This variant is not present in population databases (ExAC no frequency).

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

Last Updated: Oct 26, 2024