Submissions for variant NM_000101.4(CYBA):c.269G>C (p.Arg90Pro)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV005238653	SCV005885432	likely pathogenic	Chronic granulomatous disease	2025-02-21	criteria provided, single submitter	clinical testing	Variant summary: CYBA c.269G>C (p.Arg90Pro) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251050 control chromosomes. c.269G>C has been reported in the literature in individuals affected with Chronic Granulomatous Disease (e.g. Roos_2021). Other variants affecting the same codon have been classified as pathogenic by our lab and/or others in ClinVar (c.268C>T, p.Arg90Trp; c.269G>A, p.Arg90Gln), supporting the critical relevance of codon 90 to CYBA protein function. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 20167518, 34547651, 31847883). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as likely pathogenic.