Submissions for variant NM_025099.6(CTC1):c.248G>C (p.Ser83Thr)

dbSNP: rs78870822

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000194588	SCV000247128	benign	not specified	2015-09-19	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001080359	SCV000407622	benign	Dyskeratosis congenita	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae	RCV001080359	SCV000554103	benign	Dyskeratosis congenita	2024-01-29	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000514253	SCV000609821	likely benign	not provided	2017-07-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000514253	SCV001866187	benign	not provided	2020-11-11	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 26344056)
Genome-Nilou Lab	RCV001807135	SCV002055572	benign	Cerebroretinal microangiopathy with calcifications and cysts 1	2021-07-15	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV001080359	SCV002531284	benign	Dyskeratosis congenita	2020-02-24	criteria provided, single submitter	curation
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000194588	SCV002547587	benign	not specified	2022-05-20	criteria provided, single submitter	clinical testing	Variant summary: CTC1 c.248G>C (p.Ser83Thr) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0087 in 248724 control chromosomes, including 25 homozygotes (gnomAD). The variant occurs predominantly at a frequency of 0.01 within the Non-Finnish European subpopulation in the gnomAD database, including 6 homozygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 9 fold of the estimated maximal expected allele frequency for a pathogenic variant in CTC1 causing Cerebroretinal Microangiopathy With Calcifications And Cysts 1 phenotype (0.0011), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. To our knowledge, no occurrence of c.248G>C in individuals affected with Cerebroretinal Microangiopathy With Calcifications And Cysts 1 and no experimental evidence demonstrating its impact on protein function have been reported. Six ClinVar submitters have assessed the variant since 2014: one classified the variant as likely benign and five as benign. Based on the evidence outlined above, the variant was classified as benign.
Fulgent Genetics, Fulgent Genetics	RCV001807135	SCV002807387	benign	Cerebroretinal microangiopathy with calcifications and cysts 1	2021-07-12	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000514253	SCV002822363	likely benign	not provided	2023-12-01	criteria provided, single submitter	clinical testing	CTC1: BS2
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000514253	SCV001741588	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000194588	SCV001957812	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000514253	SCV002036110	likely benign	not provided		no assertion criteria provided	clinical testing