Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000210575 | SCV000262922 | uncertain significance | Inborn genetic diseases | 2012-10-01 | criteria provided, single submitter | clinical testing | Based on data from the NHLBI Exome Sequencing Project (ESP), the C-allele has an overall frequency of approximately 0.08% (7/9328) total alleles studied. The C-allele was observed in 0.09% (6/6454) European American alleles and in 0.03% (1/2874) African American alleles studied and was observed in the homozygous state 0 out of 4664 individuals studied (http://snp.gs.washington.edu/EVS). To our knowledge, this variant has not been reported in the SNPDatabase or in the 1000 Genome Project (Database of Single Nucleotide Polymorphisms (dbSNP). Bethesda (MD): National Center for Biotechnology Information, National Library of Medicine. (dbSNP Build ID: 135). Available from: http://www.ncbi.nlm.nih.gov/SNP. Accessed Jan 2012; 1000 Genomes Project Consortium. Nature. 2010 Oct 28;467(7319):1061-73). This amino acid position is moderately conserved in available vertebrate species.This alteration is predicted to be possibly damaging with a score of 0.708 (sensitivity: 0.78; specificity: 0.85)This alteration is predicted to be tolerated with a score of 0.250 (conservation: 1.82) |
Invitae | RCV000799119 | SCV000938768 | pathogenic | Jeune thoracic dystrophy | 2024-01-31 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 3557 of the DYNC2H1 protein (p.Ser3557Pro). This variant is present in population databases (rs200460601, gnomAD 0.04%). This missense change has been observed in individual(s) with clinical features of asphyxiating thoracic dystrophy (PMID: 23339108, 25356970, 28973083; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 225033). 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. For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV001333710 | SCV001526376 | pathogenic | Asphyxiating thoracic dystrophy 3 | 2018-07-03 | criteria provided, single submitter | clinical testing | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. |
Gene |
RCV001560184 | SCV001782541 | likely pathogenic | not provided | 2023-05-04 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25356970, 28973083, 34426522, 23339108) |