Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001228614 | SCV001401021 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2F | 2022-03-20 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with HSPB1-related conditions. This variant is present in population databases (rs147500292, gnomAD 0.01%). ClinVar contains an entry for this variant (Variation ID: 955895). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 200 of the HSPB1 protein (p.Asp200Asn). |
Ambry Genetics | RCV002356974 | SCV002657120 | uncertain significance | Inborn genetic diseases | 2020-06-15 | criteria provided, single submitter | clinical testing | The p.D200N variant (also known as c.598G>A), located in coding exon 3 of the HSPB1 gene, results from a G to A substitution at nucleotide position 598. The aspartic acid at codon 200 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Clinical Genetics, |
RCV001796398 | SCV002034662 | uncertain significance | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV001796398 | SCV002037382 | uncertain significance | not provided | no assertion criteria provided | clinical testing |