Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002999291 | SCV003295892 | uncertain significance | not provided | 2022-05-05 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1983 of the HERC1 protein (p.Arg1983Cys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with HERC1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 | RCV003007329 | SCV003552524 | uncertain significance | Inborn genetic diseases | 2021-01-27 | criteria provided, single submitter | clinical testing | The c.5947C>T (p.R1983C) alteration is located in exon 33 (coding exon 32) of the HERC1 gene. This alteration results from a C to T substitution at nucleotide position 5947, causing the arginine (R) at amino acid position 1983 to be replaced by a cysteine (C). The p.R1983C alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |