Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Institute for Human Genetics and Genomic Medicine, |
RCV001376177 | SCV001573127 | likely pathogenic | Hereditary spastic paraplegia 3A | 2021-05-05 | criteria provided, single submitter | clinical testing | To our knowledge, this sequence variant has not been reported in the literature or in control databases. However, a sequence variant affecting the same nuceotide, c.740A>C, p.(His247Pro), has previously been reported as causing SPG3 (Nameka 2006, Abel, 2004). The detected variant segregates with the disease in the family. We therefore classify it as being likely pathogenic. |
| Invitae | RCV001376177 | SCV003442284 | uncertain significance | Hereditary spastic paraplegia 3A | 2022-09-17 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the p.His247 amino acid residue in ATL1. Other variant(s) that disrupt this residue have been observed in individuals with ATL1-related conditions (PMID: 14695538), which suggests that this may be a clinically significant amino acid residue. 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. ClinVar contains an entry for this variant (Variation ID: 1065628). This missense change has been observed in individual(s) with ATL1-related conditions (PMID: 19459885, 26671083). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 247 of the ATL1 protein (p.His247Arg). |