Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000767157 | SCV000536021 | uncertain significance | not provided | 2017-01-11 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the PCNT gene. The L3055I variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The L3055I variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution occurs at a position that is conserved across species. However, the L3055I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Genetic Services Laboratory, |
RCV000435702 | SCV000596333 | uncertain significance | not specified | 2015-12-11 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000767157 | SCV002316269 | uncertain significance | not provided | 2022-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 3055 of the PCNT protein (p.Leu3055Ile). This variant is present in population databases (rs754586558, gnomAD 0.08%). 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: 392707). 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: "Tolerated"; PolyPhen-2: "Possibly 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. |
Preventiongenetics, |
RCV003418138 | SCV004107869 | uncertain significance | PCNT-related condition | 2023-07-10 | criteria provided, single submitter | clinical testing | The PCNT c.9163C>A variant is predicted to result in the amino acid substitution p.Leu3055Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.078% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/21-47858140-C-A), which may be too common to be an undocumented disease-causing variant. 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. |