NM_001081.4(CUBN):c.5305G>C (p.Val1769Leu) AND Imerslund-Gräsbeck syndrome 1

Clinical significance:Uncertain significance (Last evaluated: Jan 18, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:

Allele description [Variation Report for NM_001081.4(CUBN):c.5305G>C (p.Val1769Leu)]

NM_001081.4(CUBN):c.5305G>C (p.Val1769Leu)

CUBN:cubilin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_001081.4(CUBN):c.5305G>C (p.Val1769Leu)
  • NC_000010.11:g.16947272C>G
  • NG_008967.1:g.187546G>C
  • NM_001081.3:c.5305G>C
  • NM_001081.4:c.5305G>CMANE SELECT
  • NP_001072.2:p.Val1769Leu
  • NP_001072.2:p.Val1769Leu
  • LRG_540t1:c.5305G>C
  • LRG_540:g.187546G>C
  • LRG_540p1:p.Val1769Leu
  • NC_000010.10:g.16989271C>G
Protein change:
dbSNP: rs74116778
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001081.3:c.5305G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001081.4:c.5305G>C - missense variant - [Sequence Ontology: SO:0001583]


Imerslund-Gräsbeck syndrome 1 (IGS1)
Megaloblastic anemia 1, Finnish type; MEGALOBLASTIC ANEMIA, FINNISH TYPE
MONDO: MONDO:0100156; MedGen: C4016819; OMIM: 261100

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000361704Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Uncertain significance
(Jan 13, 2018)
germlineclinical testing

Citation Link,

SCV001521873Baylor Geneticscriteria provided, single submitter
Uncertain significance
(Jan 18, 2019)
paternalclinical testing

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

Summary from all submissions

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



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]

Details of each submission

From Illumina Clinical Services Laboratory,Illumina, SCV000361704.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided


This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

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

From Baylor Genetics, SCV001521873.1

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


This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1paternalyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 25, 2021

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