Submissions for variant NM_001081.4(CUBN):c.7837A>C (p.Ile2613Leu)

gnomAD frequency: 0.00031  dbSNP: rs144626884

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001106115	SCV001263149	uncertain significance	Imerslund-Grasbeck syndrome type 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.
Baylor Genetics	RCV001106115	SCV001528827	uncertain significance	Imerslund-Grasbeck syndrome type 1	2018-04-17	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp	RCV002069748	SCV002448352	likely benign	Imerslund-Grasbeck syndrome	2024-10-28	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV003480958	SCV004225211	uncertain significance	not provided	2022-10-06	criteria provided, single submitter	clinical testing	BP4
GeneDx	RCV003480958	SCV005383470	uncertain significance	not provided	2024-04-22	criteria provided, single submitter	clinical testing	In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign in association with a CUBN-related disorder to our knowledge; This variant is associated with the following publications: (PMID: 30900415)
PreventionGenetics, part of Exact Sciences	RCV003928707	SCV004740247	likely benign	CUBN-related disorder	2024-02-06	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).