Submissions for variant NM_000497.4(CYP11B1):c.1486del (p.Leu496fs)

dbSNP: rs1554652528

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000667414	SCV000791852	uncertain significance	Deficiency of steroid 11-beta-monooxygenase	2017-05-25	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003420179	SCV004114308	pathogenic	CYP11B1-related disorder	2022-10-07	criteria provided, single submitter	clinical testing	The CYP11B1 c.1486delC variant is predicted to result in a frameshift and premature protein termination (p.Leu497Serfs*26). This patient is heterozygous in the CYP11B1 gene for a sequence variant defined as c.1486del, which is predicted to result in a frameshift and prolonged protein (p.Leu497Serfs*26) (the normal stop codon is at codon 504). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Frameshift variants in CYP11B1 resulting in a premature protein termination or a prolonged protein are expected to be pathogenic for autosomal recessive congenital adrenal hyperplasia (CAH) due to 11-beta-hydroxylase deficiency (see prolonged protein example at Karlekar et al. 2021. PubMed ID: 33275286; Yuan et al. 2018. PubMed ID: 30241518). This variant is interpreted as pathogenic.