Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001884216 | SCV002153921 | uncertain significance | Hereditary spastic paraplegia 11 | 2022-09-29 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with asparagine, which is neutral and polar, at codon 1402 of the SPG11 protein (p.His1402Asn). This variant is present in population databases (rs756973532, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with SPG11-related conditions. ClinVar contains an entry for this variant (Variation ID: 1387758). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SPG11 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 | RCV004039044 | SCV004955043 | uncertain significance | Inborn genetic diseases | 2023-09-23 | criteria provided, single submitter | clinical testing | The c.4204C>A (p.H1402N) alteration is located in exon 25 (coding exon 25) of the SPG11 gene. This alteration results from a C to A substitution at nucleotide position 4204, causing the histidine (H) at amino acid position 1402 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |