Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000493816 | SCV000582152 | uncertain significance | not provided | 2017-05-12 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the PCNT gene. The R312W variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R312W variant is observed in 7/36,328 (0.02%) alleles from individuals of European background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R312W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Invitae | RCV000493816 | SCV002156551 | uncertain significance | not provided | 2022-10-24 | 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 312 of the PCNT protein (p.Arg312Trp). This variant is present in population databases (rs572076735, gnomAD 0.03%), including at least one homozygous and/or hemizygous individual. 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: 429553). 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"). 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. |
Fulgent Genetics, |
RCV002475975 | SCV002781370 | uncertain significance | Microcephalic osteodysplastic primordial dwarfism type II | 2021-07-12 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002524030 | SCV003610993 | uncertain significance | Inborn genetic diseases | 2021-08-10 | criteria provided, single submitter | clinical testing | The c.934C>T (p.R312W) alteration is located in exon 5 (coding exon 5) of the PCNT gene. This alteration results from a C to T substitution at nucleotide position 934, causing the arginine (R) at amino acid position 312 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Institute for Clinical Genetics, |
RCV000493816 | SCV004026167 | uncertain significance | not provided | 2021-07-05 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003419829 | SCV004107891 | uncertain significance | PCNT-related condition | 2023-12-05 | criteria provided, single submitter | clinical testing | The PCNT c.934C>T variant is predicted to result in the amino acid substitution p.Arg312Trp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.023% of alleles in individuals of European (Finnish) descent in gnomAD, including a homozygous individual. 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. |