Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002533815 | SCV003521753 | uncertain significance | not provided | 2022-07-30 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with clinical features of BLK-related conditions (PMID: 30191644). 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. Experimental studies have shown that this missense change affects BLK function (PMID: 31101814). 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. ClinVar contains an entry for this variant (Variation ID: 619202). This variant is present in population databases (rs144615291, gnomAD 0.007%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 131 of the BLK protein (p.Arg131Gln). |
Prevention |
RCV003411696 | SCV004115319 | uncertain significance | BLK-related condition | 2023-04-12 | criteria provided, single submitter | clinical testing | The BLK c.392G>A variant is predicted to result in the amino acid substitution p.Arg131Gln. This variant has reported in a cohort of patients with diabetes (Table S5, Johnson et al 2019. PubMed ID: 30191644). This variant has also been reported in a cohort of patients with systemic lupus erythematosus (SLE) (Jiang SH et al 2019. PubMed ID: 31101814). This variant is reported in 0.0077% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/8-11407691-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Carola Vinuesa Lab, |
RCV000758182 | SCV000886647 | benign | Systemic lupus erythematosus | no assertion criteria provided | research |