NM_001081.4(CUBN):c.1010C>T (p.Pro337Leu) AND none provided

Clinical significance:Likely pathogenic (Last evaluated: Feb 28, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_001081.4(CUBN):c.1010C>T (p.Pro337Leu)]

NM_001081.4(CUBN):c.1010C>T (p.Pro337Leu)

CUBN:cubilin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_001081.4(CUBN):c.1010C>T (p.Pro337Leu)
  • NC_000010.11:g.17110924G>A
  • NG_008967.1:g.23894C>T
  • NM_001081.4:c.1010C>TMANE SELECT
  • NP_001072.2:p.Pro337Leu
  • LRG_540:g.23894C>T
  • NC_000010.10:g.17152923G>A
Protein change:
P337L; PRO337LEU
OMIM: 602997.0004
Molecular consequence:
  • NM_001081.4:c.1010C>T - missense variant - [Sequence Ontology: SO:0001583]


none provided
MedGen: CN235283

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV001471240ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratoriescriteria provided, single submitter
Likely pathogenic
(Feb 28, 2020)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories, SCV001471240.1

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


The CUBN c.1010C>T; p.Pro337Leu variant (rs202153130) is reported in the literature in multiple individuals affected with a hereditary vitamin B12 deficiency syndrome (Hauck 2008, Tanner 2012). Affected individuals with this variant have each been reported to carry an additional pathogenic variant (Tanner 2012), including one individual with a partial CUBN deletion confirmed in trans to p.Pro337Leu (Hauck 2008). The p.Pro337Leu variant is found in the non-Finnish European population with an overall allele frequency of 0.02% (29/129158 alleles) in the Genome Aggregation Database. The proline at codon 337 is highly conserved and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Based on available information, this variant is considered to be likely pathogenic. References: Hauck FH et al. Imerslund-Grasbeck syndrome in a 15-year-old German girl caused by compound heterozygous mutations in CUBN. Eur J Pediatr. 2008 Jun;167(6):671-5. Tanner SM et al. Inherited cobalamin malabsorption. Mutations in three genes reveal functional and ethnic patterns. Orphanet J Rare Dis. 2012 Aug 28;7:56.

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

Last Updated: Jan 30, 2021

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