Submissions for variant NM_025099.6(CTC1):c.3604C>T (p.Arg1202Ter)

gnomAD frequency: 0.00118  dbSNP: rs147714487

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000732314	SCV000860249	uncertain significance	not provided	2018-03-07	criteria provided, single submitter	clinical testing
Invitae	RCV001081646	SCV001001757	likely benign	Dyskeratosis congenita	2024-01-29	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001330034	SCV001521624	uncertain significance	Cerebroretinal microangiopathy with calcifications and cysts 1	2019-02-11	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Genome-Nilou Lab	RCV001330034	SCV002055625	uncertain significance	Cerebroretinal microangiopathy with calcifications and cysts 1	2021-07-15	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV001816802	SCV002067333	uncertain significance	not specified	2020-07-27	criteria provided, single submitter	clinical testing	DNA sequence analysis of the CTC1 gene demonstrated a sequence change in the last exon, c.3604C>T, which results in the creation of a premature stop codon at amino acid position 1202, p.Arg1202*. This sequence change is predicted to escape nonsense mediated decay and result in the production of a truncated CTC1 protein. This sequence change has previously been described in a patient with moderate aplastic anemia in the heterozygous state (PMID: 30891747), however this sequence change has also been described in the gnomAD database with a relatively high population frequency of 0.38% in the African subpopulation (rs147714487). Due to the lack of additional studies that conclusively demonstrate the effect of this variant on protein function, the presence of this variant in a relatively high proportion of individuals in control populations, and its presence in the last exon of the gene with no other truncating variants described downstream of this variant to date, the clinical significance of the p.Arg1202* change remains unknown at this time.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV001330034	SCV002496089	uncertain significance	Cerebroretinal microangiopathy with calcifications and cysts 1	2021-09-16	criteria provided, single submitter	clinical testing	CTC1 NM_025099.5 exon 23 p.Arg1202* (c.3604C>T): This variant has been reported in the literature in 1 individual with aplastic anemia in the heterozygous state (Shen 2019 PMID:30891747). This variant is present in 0.4% of African American alleles and in 1 homozygote in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/17-8228230-G-A?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:596465). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant creates a premature stop at this codon. However, this variant occurs within the last exon of this gene; due to its position, it is possible that this protein may escape nonsense-mediated decay. Further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
GeneDx	RCV000732314	SCV004021645	uncertain significance	not provided	2023-07-20	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation as the last 16 amino acids are lost, although loss-of-function variants have not been reported downstream of this position in the protein; Observed in the germline of an individual with aplastic anemia and absent in 366 patients with myeloid disease (Shen et al., 2019); This variant is associated with the following publications: (PMID: 34426522, 30891747)