Submissions for variant NM_025099.6(CTC1):c.2959C>T (p.Arg987Trp)

gnomAD frequency: 0.00005  dbSNP: rs202138550

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000533706	SCV000631341	pathogenic	Dyskeratosis congenita	2023-11-27	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 987 of the CTC1 protein (p.Arg987Trp). This variant is present in population databases (rs202138550, gnomAD 0.009%). This missense change has been observed in individuals with Coats plus syndrome (PMID: 22267198, 22899577). ClinVar contains an entry for this variant (Variation ID: 30996). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CTC1 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects CTC1 function (PMID: 23869908, 24115768). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV001268611	SCV001447656	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000023987	SCV002055620	pathogenic	Cerebroretinal microangiopathy with calcifications and cysts 1	2021-07-15	criteria provided, single submitter	clinical testing
OMIM	RCV000023987	SCV000045278	pathogenic	Cerebroretinal microangiopathy with calcifications and cysts 1	2012-01-22	no assertion criteria provided	literature only