Submissions for variant NM_017882.3(CLN6):c.791CCT[1] (p.Ser265del)

dbSNP: rs768422260

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000727479	SCV000240689	pathogenic	not provided	2024-10-31	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32056211, 12815591, 15265688, 19520283, 19135028, 21990111, 19201763, 30705896, 31029456, 31130284, 33726816, 34426522, 29930972, 35505348, 36137348, 35796208)
Genetic Services Laboratory, University of Chicago	RCV000195031	SCV000247045	pathogenic	Ceroid lipofuscinosis, neuronal, 6A	2015-05-11	criteria provided, single submitter	clinical testing
Mendelics	RCV000989353	SCV001139644	pathogenic	Neuronal ceroid lipofuscinosis	2019-05-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000989353	SCV001410001	pathogenic	Neuronal ceroid lipofuscinosis	2024-12-09	criteria provided, single submitter	clinical testing	This variant, c.794_796del, results in the deletion of 1 amino acid(s) of the CLN6 protein (p.Ser265del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs768422260, gnomAD 0.01%). This variant has been observed in individuals with neuronal ceroid lipofuscinosis type 6 (PMID: 19135028, 19520283, 30705896, 31029456). It has also been observed to segregate with disease in related individuals. Algorithms developed to predict the effect of variants on gene product structure and function are not available or were not evaluated for this variant. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on CLN6 function (PMID: 15265688). For these reasons, this variant has been classified as Pathogenic.
Centre for Inherited Metabolic Diseases, Karolinska University Hospital	RCV000195031	SCV001571377	pathogenic	Ceroid lipofuscinosis, neuronal, 6A	2021-04-13	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000727479	SCV001713713	likely pathogenic	not provided	2019-04-07	criteria provided, single submitter	clinical testing	PP1, PM2, PM3, PM4, PS4_moderate
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV000195031	SCV001786701	likely pathogenic	Ceroid lipofuscinosis, neuronal, 6A		criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000727479	SCV002023253	likely pathogenic	not provided	2020-11-23	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV001810435	SCV002060242	pathogenic	Ceroid lipofuscinosis, neuronal, 6A; Ceroid lipofuscinosis, neuronal, 6B (Kufs type)	2021-11-10	criteria provided, single submitter	clinical testing	NM_017882.2(CLN6):c.794_796delCCT(S265del) is an in-frame deletion variant classified as pathogenic in the context of neuronal ceroid lipofuscinosis, CLN6-related. S265del has been observed in cases with relevant disease (PMID: 21990111, 12815591, 19135028, 29930972). Functional assessments of this variant are available in the literature (PMID: 19135028, 15265688). S265del has been observed in population frequency databases (gnomAD: AFR 0.01%). In summary, NM_017882.2(CLN6):c.794_796delCCT(S265del) is an in-frame deletion variant that has been observed more frequently in cases with the relevant disease than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.
CeGaT Center for Human Genetics Tuebingen	RCV000727479	SCV002497797	pathogenic	not provided	2024-08-01	criteria provided, single submitter	clinical testing	CLN6: PP4:Strong, PM2, PM3, PM4
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV000195031	SCV004806445	likely pathogenic	Ceroid lipofuscinosis, neuronal, 6A	2024-03-25	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000195031	SCV005038804	pathogenic	Ceroid lipofuscinosis, neuronal, 6A	2024-04-30	criteria provided, single submitter	clinical testing	Detected in the homozygous state in a 6 years old living girl.
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV000727479	SCV005198921	pathogenic	not provided	2022-05-27	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV001810435	SCV005630976	pathogenic	Ceroid lipofuscinosis, neuronal, 6A; Ceroid lipofuscinosis, neuronal, 6B (Kufs type)	2024-05-10	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000727479	SCV000708915	uncertain significance	not provided	2017-06-13	flagged submission	clinical testing