Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Mayo Clinic Laboratories, |
RCV000023989 | SCV000809082 | pathogenic | Cerebroretinal microangiopathy with calcifications and cysts 1 | 2018-04-09 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000798102 | SCV000937699 | pathogenic | Dyskeratosis congenita | 2024-03-22 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 259 of the CTC1 protein (p.Val259Met). This variant is present in population databases (rs387907080, gnomAD 0.006%). This missense change has been observed in individual(s) with Coats plus syndrome (PMID: 22267198, 29111009). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 30998). 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: 24115768, 29481669). For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV001577148 | SCV001804481 | likely pathogenic | not provided | 2021-01-07 | criteria provided, single submitter | clinical testing | Multiple published functional studies demonstrate a damaging effect of V259M, including abolished association with endogenous DNA polymerase alpha-primase, protein accumulation in the cytoplasm, excessive telomere loss, spontaneous chromosome breakage, severe chromosome fragmentation, reduced cellular proliferation, and poor cell survival under replication stress (Chen et al., 2013; Wang et al., 2018); This variant is associated with the following publications: (PMID: 31589614, 23220793, 22267198, 29111009, 29774655, 29481669, 24115768, 23869908, 18076099) |
Genome- |
RCV000023989 | SCV002055622 | likely pathogenic | Cerebroretinal microangiopathy with calcifications and cysts 1 | 2021-07-15 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000023989 | SCV002790998 | likely pathogenic | Cerebroretinal microangiopathy with calcifications and cysts 1 | 2021-08-18 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000023989 | SCV003835278 | pathogenic | Cerebroretinal microangiopathy with calcifications and cysts 1 | 2022-06-13 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000023989 | SCV000045280 | pathogenic | Cerebroretinal microangiopathy with calcifications and cysts 1 | 2012-01-22 | no assertion criteria provided | literature only |