ClinVar Miner

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

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001285020 SCV001471240 likely pathogenic none provided 2020-02-28 criteria provided, single submitter clinical testing 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.
OMIM RCV001095371 SCV001250979 pathogenic Imerslund-Gräsbeck syndrome 1 2020-05-18 no assertion criteria provided literature only

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