Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001037939 | SCV001201376 | uncertain significance | Niemann-Pick disease, type C1 | 2021-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine with tyrosine at codon 441 of the NPC1 protein (p.His441Tyr). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is present in population databases (rs764171713, ExAC 0.001%). This variant has not been reported in the literature in individuals affected with NPC1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. |
| Ambry Genetics | RCV002379491 | SCV002690432 | uncertain significance | Inborn genetic diseases | 2022-06-12 | criteria provided, single submitter | clinical testing | The p.H441Y variant (also known as c.1321C>T), located in coding exon 8 of the NPC1 gene, results from a C to T substitution at nucleotide position 1321. The histidine at codon 441 is replaced by tyrosine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Mayo Clinic Laboratories, |
RCV004792642 | SCV005408595 | uncertain significance | not provided | 2024-08-05 | criteria provided, single submitter | clinical testing | PM2 |