Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000147123 | SCV000194483 | uncertain significance | Microcephalic osteodysplastic primordial dwarfism type II | 2014-07-16 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000147123 | SCV000895283 | uncertain significance | Microcephalic osteodysplastic primordial dwarfism type II | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001857520 | SCV002111645 | uncertain significance | not provided | 2022-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 143 of the PCNT protein (p.Arg143Cys). This variant is present in population databases (rs201176638, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with PCNT-related conditions. ClinVar contains an entry for this variant (Variation ID: 159598). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Prevention |
RCV003398788 | SCV004105518 | uncertain significance | PCNT-related condition | 2024-01-20 | criteria provided, single submitter | clinical testing | The PCNT c.427C>T variant is predicted to result in the amino acid substitution p.Arg143Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.076% of alleles in individuals of Latino descent in gnomAD. Of note, a different variant impacting the same amino acid residue (p.Arg143His) has been reported as de novo in at least one patient with autism (Family ID 13863 in Supplemental Table 2, Iossifov. 2014. PubMed ID: 25363768; Table S2, Turner et al. 2019. PubMed ID: 31785789). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |