NM_017617.5(NOTCH1):c.3631C>T (p.Arg1211Trp) AND Adams-Oliver syndrome 5

Clinical significance:Uncertain significance (Last evaluated: Jun 17, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001219827.1

Allele description [Variation Report for NM_017617.5(NOTCH1):c.3631C>T (p.Arg1211Trp)]

NM_017617.5(NOTCH1):c.3631C>T (p.Arg1211Trp)

Gene:
NOTCH1:notch receptor 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q34.3
Genomic location:
Preferred name:
NM_017617.5(NOTCH1):c.3631C>T (p.Arg1211Trp)
HGVS:
  • NC_000009.12:g.136507317G>A
  • NG_007458.1:g.43470C>T
  • NM_017617.5:c.3631C>TMANE SELECT
  • NP_060087.3:p.Arg1211Trp
  • LRG_1122t1:c.3631C>T
  • LRG_1122:g.43470C>T
  • LRG_1122p1:p.Arg1211Trp
  • NC_000009.11:g.139401769G>A
  • NM_017617.3:c.3631C>T
Protein change:
R1211W
Links:
dbSNP: rs766644919
NCBI 1000 Genomes Browser:
rs766644919
Molecular consequence:
  • NM_017617.5:c.3631C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Adams-Oliver syndrome 5 (AOS5)
Identifiers:
MONDO: MONDO:0014459; MedGen: C4014970; Orphanet: 974; OMIM: 616028

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001391785Invitaecriteria provided, single submitter
Uncertain significance
(Jun 17, 2019)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Results of next-generation sequencing gene panel diagnostics including copy-number variation analysis in 810 patients suspected of heritable thoracic aortic disorders.

Overwater E, Marsili L, Baars MJH, Baas AF, van de Beek I, Dulfer E, van Hagen JM, Hilhorst-Hofstee Y, Kempers M, Krapels IP, Menke LA, Verhagen JMA, Yeung KK, Zwijnenburg PJG, Groenink M, van Rijn P, Weiss MM, Voorhoeve E, van Tintelen JP, Houweling AC, Maugeri A.

Hum Mutat. 2018 Sep;39(9):1173-1192. doi: 10.1002/humu.23565. Epub 2018 Jul 12.

PubMed [citation]
PMID:
29907982
PMCID:
PMC6175145

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, SCV001391785.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces arginine with tryptophan at codon 1211 of the NOTCH1 protein (p.Arg1211Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs766644919, ExAC 0.005%). This variant has been observed in an individual affected with a thoracic aortic aneurysm and dissection (PMID: 29907982). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C). 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. 5

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

Last Updated: Oct 7, 2021

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