Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002513215 | SCV003249035 | pathogenic | Dyskeratosis congenita | 2021-12-24 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Experimental studies have shown that this missense change affects CTC1 function (PMID: 24115768, 29481669). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 31004). This missense change has been observed in individual(s) with cerebroretinal microangiopathy with calcifications and cysts (PMID: 22387016). 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. This variant is present in population databases (rs199473673, gnomAD 0.2%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 227 of the CTC1 protein (p.Ala227Val). |
OMIM | RCV000023995 | SCV000045286 | pathogenic | Cerebroretinal microangiopathy with calcifications and cysts 1 | 2012-03-09 | no assertion criteria provided | literature only |