Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV005682603 | SCV006378351 | uncertain significance | Inborn genetic diseases | 2025-08-27 | criteria provided, single submitter | clinical testing | The c.434A>C (p.H145P) alteration is located in exon 1 (coding exon 1) of the NHLRC1 gene. This alteration results from a A to C substitution at nucleotide position 434, causing the histidine (H) at amino acid position 145 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001315366 | SCV001505935 | uncertain significance | Lafora disease | 2020-09-07 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine with proline at codon 145 of the NHLRC1 protein (p.His145Pro). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NHLRC1-related conditions. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |