Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000472493 | SCV000548842 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2O | 2020-01-28 | criteria provided, single submitter | clinical testing | In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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, but these predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a DYNC1H1-related disease. This sequence change replaces histidine with tyrosine at codon 2171 of the DYNC1H1 protein (p.His2171Tyr). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and tyrosine. |
| Ambry Genetics | RCV002365637 | SCV002659209 | uncertain significance | Inborn genetic diseases | 2020-02-20 | criteria provided, single submitter | clinical testing | The p.H2171Y variant (also known as c.6511C>T), located in coding exon 32 of the DYNC1H1 gene, results from a C to T substitution at nucleotide position 6511. The histidine at codon 2171 is replaced by tyrosine, an amino acid with similar properties. This amino acid position is well 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. |