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

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Mar 11, 2019
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:
RCV001249691.12

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:
Myhre syndrome (MYHRS)
Synonyms:
Growth mental deficiency syndrome of Myhre; LARYNGOTRACHEAL STENOSIS, ARTHROPATHY, PROGNATHISM, AND SHORT STATURE; LAPS SYNDROME
Identifiers:
MONDO: MONDO:0007688; MedGen: C0796081; Orphanet: 2588; OMIM: 139210
Name:
Generalized juvenile polyposis/juvenile polyposis coli
Synonyms:
Juvenile polyposis coli
Identifiers:
MONDO: MONDO:0008276; MedGen: C1868081; Orphanet: 329971
Name:
Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome (JPHT)
Synonyms:
JP/HHT SYNDROME; JUVENILE POLYPOSIS WITH HEREDITARY HEMORRHAGIC TELANGIECTASIA; POLYPOSIS, GENERALIZED JUVENILE, WITH PULMONARY ARTERIOVENOUS MALFORMATION; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008278; MedGen: C1832942; Orphanet: 2929; OMIM: 175050

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001423686Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Mar 11, 2019) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot 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 Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital, SCV001423686.1

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

Description

[ACMG/AMP: PS2, PS3, PM1, PM2, PM5, PP2, PP3, PP5] This alteration is de novo in origin as it was not detected in the submitted parental specimens (identity confirmed) [PS2], is supported by well-established in vitro or in vivo functional studies to have a damaging effect on protein function or splicing [PS3], is located in a mutational hotspot and/or critical and well-established functional domain [PM1], is absent from or rarely observed in large-scale population databases [PM2], is a novel missense change at an amino residue where a different missense change has been deemed to be pathogenic [PM5], is a missense variant in a gene in which missense variants are a common mechanism of disease [PP2], is predicted to be damaging by multiple functional prediction tools [PP3], was reported as a pathogenic/likely pathogenic alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory) [PP5].

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

Last Updated: Nov 24, 2024