Submissions for variant NM_000104.4(CYP1B1):c.1200_1209dup (p.Thr404fs)

dbSNP: rs587778873

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000480224	SCV000339048	pathogenic	not provided	2016-01-15	criteria provided, single submitter	clinical testing
GeneDx	RCV000480224	SCV000567591	pathogenic	not provided	2021-08-02	criteria provided, single submitter	clinical testing	Frameshift variant in the C-terminus predicted to result in protein truncation, as the last 140 amino acids are replaced by 29 incorrect amino acids; This variant is associated with the following publications: (PMID: 17361544, 31589614, 25836661, 30820150, 32499604, 32832252, 26689913, 17591938, 19234632, 27272408, 9497261, 12036985, 14729846, 11558822, 12567107, 16735994, 24281366, 27508083, 28448622, 23922489, 30484747, 25750510)
Invitae	RCV002228168	SCV000813660	pathogenic	Congenital glaucoma	2024-01-09	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Thr404Serfs*30) in the CYP1B1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 140 amino acid(s) of the CYP1B1 protein. This variant is present in population databases (rs587778873, gnomAD 0.06%). This premature translational stop signal has been observed in individuals with Peters anomaly and primary congenital glaucoma (PMID: 9497261, 17591938, 19234632, 23922489, 24281366, 27272408, 28448622). It has also been observed to segregate with disease in related individuals. This variant is also known as c.1546dup10, c.1571_1580dup, and c.1198_1207dup. ClinVar contains an entry for this variant (Variation ID: 68466). For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV000480224	SCV001247368	pathogenic	not provided	2021-06-01	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000480224	SCV001446983	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000480224	SCV002018105	pathogenic	not provided	2022-02-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002477209	SCV002777793	pathogenic	Glaucoma 3A; Glaucoma 3, primary infantile, B; Anterior segment dysgenesis 6	2022-02-25	criteria provided, single submitter	clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV001250448	SCV003808004	pathogenic	Glaucoma 3A	2023-01-31	criteria provided, single submitter	clinical testing	ACMG classification criteria: PVS1 strong, PM3 very strong, PP1 supporting
PreventionGenetics, part of Exact Sciences	RCV004537264	SCV004120085	pathogenic	CYP1B1-related disorder	2023-04-20	criteria provided, single submitter	clinical testing	The CYP1B1 c.1200_1209dup10 variant is predicted to result in a frameshift and premature protein termination (p.Thr404Serfs*30). This variant has been reported along with a second causative variant in CYP1B1 in patients with congenital glaucoma and additional systemic anomalies, Peters anomaly, and/or anterior polar cataracts (see for examples Reis et al. 2016. PubMed ID: 27272408; Prokudin et al. 2014. PubMed ID: 24281366; García-Antón et al. 2017. PubMed ID: 28448622). This variant is reported in 0.068% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-38298287-T-TGGTGGCATGA). Frameshift variants in CYP1B1 are expected to be pathogenic, and this variant has been classified as pathogenic by multiple independent submitters to the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/68466). Given all the evidence, we interpret c.1200_1209dup (p.Thr404Serfs*30) as pathogenic.
Baylor Genetics	RCV003466929	SCV004215452	pathogenic	Anterior segment dysgenesis 6	2023-10-25	criteria provided, single submitter	clinical testing
OMIM	RCV001250448	SCV000028375	pathogenic	Glaucoma 3A	1998-03-01	no assertion criteria provided	literature only
Eye Genetics Research Group, Children's Medical Research Institute	RCV000059336	SCV000087412	pathogenic	Irido-corneo-trabecular dysgenesis	2012-03-30	no assertion criteria provided	research
Eye Genetics Research Group, Children's Medical Research Institute	RCV001200040	SCV001370532	pathogenic	Anterior segment dysgenesis	2020-03-31	no assertion criteria provided	clinical testing
Institute of Medical Molecular Genetics, University of Zurich	RCV001250448	SCV001424836	pathogenic	Glaucoma 3A	2019-08-01	no assertion criteria provided	research