Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002456497 | SCV002614436 | uncertain significance | Inborn genetic diseases | 2020-12-03 | criteria provided, single submitter | clinical testing | The c.337G>A (p.A113T) alteration is located in exon 1 (coding exon 1) of the NHLRC1 gene. This alteration results from a G to A substitution at nucleotide position 337, causing the alanine (A) at amino acid position 113 to be replaced by a threonine (T). The p.A113T alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001345980 | SCV001540137 | uncertain significance | Lafora disease | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with threonine at codon 113 of the NHLRC1 protein (p.Ala113Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with NHLRC1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine 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. |