Submissions for variant NM_001023570.4(IQCB1):c.1518_1519del (p.His506fs)

dbSNP: rs398123538

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000790716	SCV000226048	pathogenic	not provided	2013-06-21	criteria provided, single submitter	clinical testing
Undiagnosed Diseases Network, NIH	RCV000174695	SCV000746673	pathogenic	Senior-Loken syndrome 5	2017-05-23	criteria provided, single submitter	clinical testing	The paternally-inherited c.1518_1519delCA is a frameshift variant, which is predicted to result in loss of function in the IQCB1 gene where loss of function is a known mechanism of Senior-Loken syndrome 5, OMIM 609254. The c.1518_1519delCA variant was observed to be in trans with a c.1465C>T pathogenic variant based on segregation analysis in the family. Both varaints are also present in the patient's similarly affected sister.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001042285	SCV001205960	pathogenic	Nephronophthisis	2025-02-03	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.His506Glnfs*13) in the IQCB1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 93 amino acid(s) of the IQCB1 protein. This variant is present in population databases (rs398123538, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with Senior-Loken syndrome or Leber congenital amaurosis (PMID: 15723066, 20881296). For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000790716	SCV001447600	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Ocular Genomics Institute, Massachusetts Eye and Ear	RCV000174695	SCV001573597	pathogenic	Senior-Loken syndrome 5	2021-04-08	criteria provided, single submitter	research	The IQCB1 c.1518_1519del variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PVS1, PM3, PP1. Based on this evidence we have classified this variant as Pathogenic.
3billion, Medical Genetics	RCV000174695	SCV002058927	pathogenic	Senior-Loken syndrome 5	2022-01-03	criteria provided, single submitter	clinical testing	Frameshift: predicted to result in a loss or disruption of normal protein function through protein truncation. Multiple pathogenic variants are reported in the predicted truncated region (PVS1_VS) The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000093469, PMID:15723066). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000085, PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Baylor Genetics	RCV000174695	SCV004197973	pathogenic	Senior-Loken syndrome 5	2024-03-22	criteria provided, single submitter	clinical testing
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV004815004	SCV005073639	pathogenic	Retinal dystrophy	2020-01-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000174695	SCV005657305	pathogenic	Senior-Loken syndrome 5	2024-02-05	criteria provided, single submitter	clinical testing
Daryl Scott Lab, Baylor College of Medicine	RCV000174695	SCV005871249	pathogenic	Senior-Loken syndrome 5	2024-01-01	criteria provided, single submitter	clinical testing	PVS1, PS4, PM3, PP1
OMIM	RCV000174695	SCV000045047	pathogenic	Senior-Loken syndrome 5	2011-01-01	no assertion criteria provided	literature only
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet	RCV000787844	SCV000926858	likely pathogenic	Retinitis pigmentosa	2018-04-01	no assertion criteria provided	research
PreventionGenetics, part of Exact Sciences	RCV004755762	SCV005362129	pathogenic	IQCB1-related disorder	2024-05-07	no assertion criteria provided	clinical testing	The IQCB1 c.1518_1519delCA variant is predicted to result in a frameshift and premature protein termination (p.His506Glnfs*13). This variant has been reported to be pathogenic for Senior-Loken syndrome (see for example at Otto et al. 2005. PubMed ID: 15723066; Barbelanne et al. 2013. PubMed ID: 23446637; Sallum et al. 2020. PubMed ID: 32865313). This variant is reported in 0.017% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Frameshift variants in IQCB1 are expected to be pathogenic. This variant is interpreted as pathogenic.