Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000649560 | SCV000771389 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2O | 2023-12-28 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 4038 of the DYNC1H1 protein (p.Asn4038His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DYNC1H1-related conditions. ClinVar contains an entry for this variant (Variation ID: 539770). 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 DYNC1H1 protein function with a negative predictive value of 95%. 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. |
Gene |
RCV001731841 | SCV001983245 | uncertain significance | not provided | 2021-09-24 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function |
Ambry Genetics | RCV003258909 | SCV003983028 | uncertain significance | Inborn genetic diseases | 2023-05-22 | criteria provided, single submitter | clinical testing | The c.12112A>C (p.N4038H) alteration is located in exon 66 (coding exon 66) of the DYNC1H1 gene. This alteration results from a A to C substitution at nucleotide position 12112, causing the asparagine (N) at amino acid position 4038 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Prevention |
RCV003392494 | SCV004121017 | uncertain significance | DYNC1H1-related condition | 2022-10-21 | criteria provided, single submitter | clinical testing | The DYNC1H1 c.12112A>C variant is predicted to result in the amino acid substitution p.Asn4038His. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |