Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001080434 | SCV000255225 | likely benign | Charcot-Marie-Tooth disease type 4 | 2019-12-31 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000236667 | SCV000292668 | likely benign | not specified | 2017-11-10 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
EGL Genetic Diagnostics, |
RCV000416164 | SCV000333623 | uncertain significance | not provided | 2015-08-13 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000416164 | SCV000493486 | likely benign | not provided | 2020-01-01 | criteria provided, single submitter | clinical testing | |
Athena Diagnostics Inc | RCV000236667 | SCV000614799 | likely benign | not specified | 2016-09-06 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV001283041 | SCV001157479 | uncertain significance | none provided | 2020-08-26 | criteria provided, single submitter | clinical testing | The PRX c.2254G>A; p.Glu752Lys variant (rs147587689), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 216834). This variant is found in the general population with an allele frequency of 0.14 % (383 /282,174 alleles, including 1 homozygotes) in the Genome Aggregation Database. The glutamic acid at codon 752 is moderately conserved, and computational analyses (SIFT: tolerated, PolyPhen-2: possibly damaging) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the p.Glu752Lys variant is uncertain at this time. Pathogenic variants in PRX are associated with autosomal recessive Charcot-Marie-Tooth disease, type 4F (MIM: 614895) and Dejerine-Sottas disease (MIM: 145900). As no other significant variants were detected in the PRX gene, even if the p.Glu752Lys variant is later determined to be pathogenic, it alone is likely not causative for this patient’s symptoms. However, deep intronic variants, variants in the enhancer region, and large deletions and duplications are not analyzed by this method; therefore, additional variants in these regions cannot be ruled out. |
Illumina Clinical Services Laboratory, |
RCV001129129 | SCV001288627 | uncertain significance | Charcot-Marie-Tooth disease, demyelinating, type 4F | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Molecular Genetics Laboratory, |
RCV001172781 | SCV001335849 | likely benign | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing |