Submissions for variant NM_025099.6(CTC1):c.1728G>A (p.Pro576=)

gnomAD frequency: 0.00083  dbSNP: rs78320653

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000634522	SCV000407609	likely benign	Dyskeratosis congenita	2018-01-13	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Genetic Services Laboratory, University of Chicago	RCV000503687	SCV000594247	likely benign	not specified	2016-05-05	criteria provided, single submitter	clinical testing
Invitae	RCV000634522	SCV000755838	benign	Dyskeratosis congenita	2024-01-29	criteria provided, single submitter	clinical testing
GeneDx	RCV001753785	SCV001985661	uncertain significance	not provided	2019-04-18	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar with conflicting classifications but additional evidence is not available (SCV000407609.2, SCV000594247.1, SCV000755838.1; Landrum et al., 2016); In silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.
Genome-Nilou Lab	RCV001807228	SCV002055636	likely benign	Cerebroretinal microangiopathy with calcifications and cysts 1	2021-07-15	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000634522	SCV002531265	uncertain significance	Dyskeratosis congenita	2022-02-24	criteria provided, single submitter	curation
CeGaT Center for Human Genetics Tuebingen	RCV001753785	SCV004141945	likely benign	not provided	2023-05-01	criteria provided, single submitter	clinical testing	CTC1: BP4, BP7
PreventionGenetics, part of Exact Sciences	RCV003912360	SCV004736985	likely benign	CTC1-related condition	2021-07-14	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).