Submissions for variant NM_001256789.3(CACNA1F):c.3133dup (p.Leu1045fs)

dbSNP: rs80359870

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000790658	SCV000334438	pathogenic	not provided	2015-09-02	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000790658	SCV001247593	pathogenic	not provided	2019-05-01	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000790658	SCV001447326	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Invitae	RCV000790658	SCV001588982	pathogenic	not provided	2023-12-29	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu1056Profs*11) in the CACNA1F gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CACNA1F are known to be pathogenic (PMID: 9662399, 11281458, 17525176, 22194652, 24124559, 26992781). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with X-linked congenital stationary night blindness (PMID: 9662399, 9662400, 10900517). It is commonly reported in individuals of Mennonite ancestry (PMID: 9662399, 9662400, 10900517). This variant is also known as 3133inC, Leu991insC, and Leu1056insC. ClinVar contains an entry for this variant (Variation ID: 21443). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV000790658	SCV001790147	pathogenic	not provided	2022-02-01	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; Common pathogenic variant among individuals of Dutch-German Mennonite background (Bech-Hansen et al., 1998); Not observed at significant frequency in large population cohorts (gnomAD); Also known as L991insC using alternate nomenclature; This variant is associated with the following publications: (PMID: 9662399, 28162000, 10900517, 18348259, 22744390, 33668843, 20301423, 9662400)
MGZ Medical Genetics Center	RCV000020629	SCV002580093	pathogenic	Congenital stationary night blindness 2A	2022-06-08	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000020629	SCV004032251	pathogenic	Congenital stationary night blindness 2A	2023-08-24	criteria provided, single submitter	clinical testing	Criteria applied: PVS1,PS4_MOD,PM2_SUP
PreventionGenetics, part of Exact Sciences	RCV003398551	SCV004121492	pathogenic	CACNA1F-related disorder	2023-05-02	criteria provided, single submitter	clinical testing	The CACNA1F c.3166dupC variant is predicted to result in a frameshift and premature protein termination (p.Leu1056Profs*11). This variant has been reported in multiple individuals with congenital stationary night blindness (see for example Vincent and Héon et al. 2012. PubMed ID: 22744390; reported as c.3133insC in Strom et al. 1998. PubMed ID: 9662399). Frameshift variants in CACNA1F 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/21443). Given all the evidence, we interpret c.3166dup (p.Leu1056Profs*11) as pathogenic.
OMIM	RCV000020629	SCV000032616	pathogenic	Congenital stationary night blindness 2A	1998-07-01	no assertion criteria provided	literature only
GeneReviews	RCV000020629	SCV000041144	pathologic	Congenital stationary night blindness 2A	2012-04-26	no assertion criteria provided	curation	Converted during submission to Pathogenic.