Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001350255 | SCV001544643 | uncertain significance | not provided | 2022-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1130 of the POLR3A protein (p.Val1130Ile). This variant is present in population databases (rs199581222, gnomAD 0.09%). This variant has not been reported in the literature in individuals affected with POLR3A-related conditions. ClinVar contains an entry for this variant (Variation ID: 816787). 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 not expected to disrupt POLR3A protein function. 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. |
Ambry Genetics | RCV002549268 | SCV003756351 | uncertain significance | Inborn genetic diseases | 2022-07-27 | criteria provided, single submitter | clinical testing | The c.3388G>A (p.V1130I) alteration is located in exon 26 (coding exon 26) of the POLR3A gene. This alteration results from a G to A substitution at nucleotide position 3388, causing the valine (V) at amino acid position 1130 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Gene |
RCV001350255 | SCV004012470 | uncertain significance | not provided | 2023-06-07 | criteria provided, single submitter | clinical testing | Reported previously in the homozygous state in a patient with multiple joint contractures, delayed motor milestones, dysmorphic features, and cerebellar vermis hypoplasia who also had a homozygous variant in another gene thought to be likely related to the arthrogryposis; parents were found to be carriers but no clinical information was provided (Bayram et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 26752647, 36385762) |
Lupski Lab, |
RCV001007775 | SCV001167459 | uncertain significance | Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome | no assertion criteria provided | research |