Submissions for variant NM_001081.4(CUBN):c.9053A>C (p.Tyr3018Ser)

gnomAD frequency: 0.00009  dbSNP: rs370778353

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Mendelics	RCV000625649	SCV001138006	uncertain significance	Imerslund-Grasbeck syndrome	2019-05-28	criteria provided, single submitter	clinical testing
Molecular Biology Laboratory, Fundació Puigvert	RCV001095374	SCV001425076	likely pathogenic	Proteinuria, chronic benign	2020-02-01	criteria provided, single submitter	research
Invitae	RCV000625649	SCV002252730	uncertain significance	Imerslund-Grasbeck syndrome	2022-04-18	criteria provided, single submitter	clinical testing	This sequence change replaces tyrosine, which is neutral and polar, with serine, which is neutral and polar, at codon 3018 of the CUBN protein (p.Tyr3018Ser). This variant is present in population databases (rs370778353, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of genetic kidney disease (PMID: 31613795, 33532864). ClinVar contains an entry for this variant (Variation ID: 522507). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
AiLife Diagnostics, AiLife Diagnostics	RCV002223233	SCV002501322	likely pathogenic	not provided	2022-02-10	criteria provided, single submitter	clinical testing
Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare	RCV000625649	SCV000746152	uncertain significance	Imerslund-Grasbeck syndrome	2017-10-09	no assertion criteria provided	clinical testing
OMIM	RCV001095374	SCV001250982	affects	Proteinuria, chronic benign	2020-05-19	no assertion criteria provided	literature only