ClinVar Miner

Submissions for variant NM_006363.6(SEC23B):c.1489C>T (p.Arg497Cys)

gnomAD frequency: 0.00004  dbSNP: rs727504145
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000153928 SCV000203545 pathogenic not provided 2014-01-23 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000779341 SCV000915934 pathogenic Congenital dyserythropoietic anemia, type II 2018-10-31 criteria provided, single submitter clinical testing The SEC23B c.1489C>T (p.Arg497Cys) variant has been reported in five studies and in a total of nine individuals with dyserythropoietic anemia including one individual in a homozygous state and eight individuals in a compound heterozygous state (Schwarz et al. 2009, Bianchi et al. 2009, Iolascon et al. 2010, Russo et al. 2010, Russo et al. 2013). The variant was absent from 407 controls and is reported at a frequency of 0.000032 in the European (non-Finnish) population of the Genome Aggregation Database. The Arg497 amino acid residue is conserved among several species. Based on the evidence, the p.Arg497Cys variant is classified as pathogenic for congenital dyserythropoietic anemia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Revvity Omics, Revvity RCV000153928 SCV002019160 pathogenic not provided 2023-07-28 criteria provided, single submitter clinical testing
Invitae RCV001850108 SCV002237003 pathogenic Congenital dyserythropoietic anemia, type II; Cowden syndrome 7 2023-12-30 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 497 of the SEC23B protein (p.Arg497Cys). This variant is present in population databases (rs727504145, gnomAD 0.006%). This missense change has been observed in individual(s) with congenital dyserythropoietic anemia type II (PMID: 19561605, 19621418, 20015893, 27471141). ClinVar contains an entry for this variant (Variation ID: 167667). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SEC23B protein function. For these reasons, this variant has been classified as Pathogenic.

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