Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
EGL Genetic Diagnostics, |
RCV000081407 | SCV000113338 | pathogenic | not provided | 2013-11-18 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000688348 | SCV000815954 | pathogenic | Congenital dyserythropoietic anemia, type II; Cowden syndrome 7 | 2018-08-14 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with lysine at codon 109 of the SEC23B protein (p.Glu109Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs121918221, ExAC 0.06%). This is the most common variant associated with congenital dyserythropoietic anemia type II, which many homozygous affected individuals reported (PMID: 19561605, 19621418, 20015893, 21252497, 21850656, 25044164). ClinVar contains an entry for this variant (Variation ID: 1222). Experimental studies have shown that this missense change destabilizes the protein in cell culture (PMID: 19561605). For these reasons, this variant has been classified as Pathogenic. |
Illumina Clinical Services Laboratory, |
RCV000001281 | SCV000915932 | pathogenic | Congenital dyserythropoietic anemia, type II | 2018-10-05 | criteria provided, single submitter | clinical testing | The SEC23B c.325G>A (p.Glu109Lys) variant has been reported in at least three studies and is found in a total of 25 individuals including 23 in a homozygous state and two in a compound heterozygous state with congenital dyserythropoietic anemia (Schwarz et al. 2009; Bianchi et al. 2009; Punzo et al. 2011; Amir et al. 2011). The p.Glu109Lys variant is described as a founder mutation among the Israeli Moroccan Jewish population (Amir et al. 2011). Control data are unavailable for this variant, which is reported at a frequency of 0.000577 in the African population of the Exome Aggregation Consortium. Expression analysis in HeLa-Kyoto cells determined the p.Glu109Lys variant had less than 5% of wildtype expression (Schwarz et al. 2009). Based on the evidence, the p.Glu109Lys 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. |
OMIM | RCV000001281 | SCV000021431 | pathogenic | Congenital dyserythropoietic anemia, type II | 2009-09-01 | no assertion criteria provided | literature only |