Submissions for variant NM_001023570.4(IQCB1):c.424_425del (p.Phe142fs)

dbSNP: rs750962965

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000001905	SCV000915984	pathogenic	Senior-Loken syndrome 5	2017-04-28	criteria provided, single submitter	clinical testing	The IQCB1 c.424_425delTT (p.Phe142ProfsTer5) variant is a frameshift variant that is predicted to result in premature termination of the protein. The p.Phe142ProfsTer5 variant has been reported in three studies in which it is found in a total of nine individuals with Senior Loken syndrome, including in seven patients in a homozygous state and in two patients in a compound heterozygous state who both carried a null variant on the second allele (Otto et al. 2005; Estrada-Cuzcano et al. 2011; Halbritter et al. 2013). The p.Phe142ProfsTer5 variant was absent from 347 control subjects but is reported at a frequency of 0.00023 in the European (non-Finnish) population of the Exome Aggregation Consortium. Based on the evidence, the p.Phe142ProfsTer5 variant is classified as pathogenic for Senior Loken syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000822567	SCV000963376	pathogenic	Nephronophthisis	2025-01-13	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Phe142Profs*5) in the IQCB1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in IQCB1 are known to be pathogenic (PMID: 15723066, 21901789, 23559409, 28041643). This variant is present in population databases (rs750962965, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with Leber congenital amaurosis and Senior-L√∏ken syndrome (PMID: 15723066, 20881296, 21866095, 23188109, 24625443, 28041643, 28832562). This variant is also known as c.224_225delTT, p.F142fsX146. ClinVar contains an entry for this variant (Variation ID: 1831). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics	RCV001073766	SCV001239326	pathogenic	Retinal dystrophy	2017-12-06	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001093170	SCV001250020	pathogenic	not provided	2018-05-01	criteria provided, single submitter	clinical testing
Ocular Genomics Institute, Massachusetts Eye and Ear	RCV000001905	SCV001573560	pathogenic	Senior-Loken syndrome 5	2021-04-08	criteria provided, single submitter	research	The IQCB1 c.424_425del 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, PM2, PM3. Based on this evidence we have classified this variant as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV001093170	SCV001762005	pathogenic	not provided	2021-06-17	criteria provided, single submitter	clinical testing
GeneDx	RCV001093170	SCV001824779	pathogenic	not provided	2021-11-23	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 23446637, 21866095, 15723066, 28832562, 20881296, 29453417, 31980526, 32581362)
Fulgent Genetics, Fulgent Genetics	RCV000001905	SCV002813901	pathogenic	Senior-Loken syndrome 5	2024-05-08	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000001905	SCV004192436	pathogenic	Senior-Loken syndrome 5	2024-03-25	criteria provided, single submitter	clinical testing
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV001073766	SCV005068612	pathogenic	Retinal dystrophy	2021-01-01	criteria provided, single submitter	clinical testing
OMIM	RCV000001905	SCV000022063	pathogenic	Senior-Loken syndrome 5	2011-02-11	no assertion criteria provided	literature only
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000505085	SCV000598854	pathogenic	Leber congenital amaurosis	2015-01-01	no assertion criteria provided	research
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000001905	SCV000804661	pathogenic	Senior-Loken syndrome 5	2016-09-01	no assertion criteria provided	clinical testing