Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000195758 | SCV000254666 | uncertain significance | Jeune thoracic dystrophy | 2022-09-16 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 592 of the DYNC2H1 protein (p.Leu592Phe). This variant is present in population databases (rs180861816, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with DYNC2H1-related conditions. ClinVar contains an entry for this variant (Variation ID: 216489). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DYNC2H1 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. |
Illumina Laboratory Services, |
RCV001106879 | SCV001263988 | uncertain significance | Asphyxiating thoracic dystrophy 3 | 2018-01-13 | 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. |
Gene |
RCV001561120 | SCV001783658 | uncertain significance | not provided | 2023-06-29 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 34490615, 36011280) |
Blueprint Genetics | RCV001561120 | SCV001832475 | uncertain significance | not provided | 2019-11-30 | criteria provided, single submitter | clinical testing | |
Al Jalila Children's Genomics Center, |
RCV001106879 | SCV001984082 | uncertain significance | Asphyxiating thoracic dystrophy 3 | 2020-03-25 | criteria provided, single submitter | clinical testing | |
Genome |
RCV001249319 | SCV001423283 | not provided | DYNC2H1-Related Disorder | no assertion provided | phenotyping only | Variant interpretted as Uncertain significance and reported on 12-11-2017 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. | |
Centre de Biologie Pathologie Génétique, |
RCV001251983 | SCV001427729 | uncertain significance | Intellectual disability | 2019-01-01 | no assertion criteria provided | clinical testing | |
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV001561120 | SCV001954257 | uncertain significance | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV001561120 | SCV001971742 | uncertain significance | not provided | no assertion criteria provided | clinical testing |