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NM_005359.6(SMAD4):c.1498A>G (p.Ile500Val) AND Generalized juvenile polyposis/juvenile polyposis coli

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 27, 2018
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:
RCV000635427.14

Allele description [Variation Report for NM_005359.6(SMAD4):c.1498A>G (p.Ile500Val)]

NM_005359.6(SMAD4):c.1498A>G (p.Ile500Val)

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.1498A>G (p.Ile500Val)
Other names:
p.I500V:ATA>GTA
HGVS:
  • NC_000018.10:g.51078306A>G
  • NG_013013.2:g.115267A>G
  • NM_005359.6:c.1498A>GMANE SELECT
  • NP_005350.1:p.Ile500Val
  • NP_005350.1:p.Ile500Val
  • LRG_318t1:c.1498A>G
  • LRG_318:g.115267A>G
  • LRG_318p1:p.Ile500Val
  • NC_000018.9:g.48604676A>G
  • NM_005359.3:c.1498A>G
  • NM_005359.5:c.1498A>G
  • Q13485:p.Ile500Val
Protein change:
I500V; ILE500VAL
Links:
UniProtKB: Q13485#VAR_067604; UniProtKB/Swiss-Prot: VAR_067604; OMIM: 600993.0016; dbSNP: rs281875322
NCBI 1000 Genomes Browser:
rs281875322
Molecular consequence:
  • NM_005359.6:c.1498A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Generalized juvenile polyposis/juvenile polyposis coli
Synonyms:
Juvenile polyposis coli
Identifiers:
MONDO: MONDO:0008276; MedGen: C1868081; Orphanet: 329971

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000840072Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Apr 27, 2018) 		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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine, SCV000840072.1

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

Description

SMAD4, c.1498A>G, p.Ile500Val The c.1498A>G (p. Ile500Val) variant in the SMAD4 gene has been reported in multiple individuals with MYRHE syndrome (PMID 22158539, 22243968, 22585601, 24398790, 26636501, 27302097). This variant is observed with an ultra-low minor allele frequency in the gnomAD database (1/246232). This variant is on a known mutation hot spot with another pathogenic variant p.Ile500Thr. Functional studies on this variant suggested increased SMAD4 protein levels and increased TGF-beta signaling (PMID 24398790). Therefore, the c.1498A>G (p. Ile500Val) variant in the SMAD4 gene is classified as pathogenic

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

Last Updated: Nov 24, 2024