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NM_001081.4(CUBN):c.2452G>A (p.Gly818Arg) AND Imerslund-Grasbeck syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jun 19, 2021
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:
RCV001976248.7

Allele description

NM_001081.4(CUBN):c.2452G>A (p.Gly818Arg)

Gene:
CUBN:cubilin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10p13
Genomic location:
Preferred name:
NM_001081.4(CUBN):c.2452G>A (p.Gly818Arg)
HGVS:
  • NC_000010.11:g.17071599C>T
  • NG_008967.1:g.63219G>A
  • NM_001081.4:c.2452G>AMANE SELECT
  • NP_001072.2:p.Gly818Arg
  • LRG_540:g.63219G>A
  • NC_000010.10:g.17113598C>T
Protein change:
G818R
Links:
dbSNP: rs141274853
NCBI 1000 Genomes Browser:
rs141274853
Molecular consequence:
  • NM_001081.4:c.2452G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Imerslund-Grasbeck syndrome
Synonyms:
Megaloblastic anemia due to inborn errors of metabolism; Pernicious anemia, juvenile, due to selective intestinal malabsorption of vitamin b12, with proteinuria; Enterocyte cobalamin malabsorption; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009853; MedGen: C4551825; Orphanet: 35858; OMIM: PS261100

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002264696Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jun 19, 2021) 		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 Invitae, SCV002264696.4

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

Description

This sequence change replaces glycine with arginine at codon 818 of the CUBN protein (p.Gly818Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CUBN-related conditions. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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

Last Updated: May 1, 2024