ClinVar Miner

Submissions for variant NM_001081.3(CUBN):c.8894T>C (p.Phe2965Ser) (rs117620008)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000508534 SCV000603274 uncertain significance none provided 2019-12-18 criteria provided, single submitter clinical testing The p.Phe2965Ser variant (rs117620008) has not been reported in the medical literature, or gene specific variation databases. This variant is listed in the NHLBI GO Exome Sequencing Project with an overall population frequency of 0.22 percent (identified on 28 out of 13,006 chromosomes) and is listed in the Exome Aggregation Consortium Browser with an overall population frequency of 0.154 percent (identified on 186 out of 120,840 chromosomes). The phenylalanine at position 2965 is highly conserved (up to Cow, considering 10 species) (Alamut v.2.8.1) and computational analyses of the effects of the p.Phe2965Ser variant on protein structure and function predict a deleterious effect (SIFT: damaging, MutationTaster: disease causing, PolyPhen-2: possibly damaging). Altogether, there is not enough evidence to classify the p.Phe2965Ser variant with certainty.
GeneDx RCV000766837 SCV000616693 uncertain significance not provided 2017-07-31 criteria provided, single submitter clinical testing The F2965S variant in the CUBN gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The F2965S variant is observed in 167/66388 (0.25%) alleles from individuals of non-Finnish European background, in the ExAC dataset (Lek et al., 2016). The F2965S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret F2965S as a variant of uncertain significance.
Invitae RCV001029961 SCV001001737 likely benign Imerslund-Gräsbeck syndrome 2020-11-06 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001106016 SCV001263040 uncertain significance Imerslund-Gräsbeck syndrome 1 2018-01-12 criteria provided, single submitter clinical testing 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.
Bioscientia Institut fuer Medizinische Diagnostik GmbH,Sonic Healthcare RCV001029961 SCV001192759 uncertain significance Imerslund-Gräsbeck syndrome 2019-07-25 no assertion criteria provided clinical testing

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