Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000779162 | SCV000915678 | uncertain significance | Hereditary spastic paraplegia 11 | 2017-09-15 | criteria provided, single submitter | clinical testing | The SPG11 c.4746_4747insTG (p.Asn1583Ter) variant results in a frameshift, and is predicted to result in premature termination of the protein. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. Based on the variant frequency, disease prevalence, disease penetrance, and inheritance mode, this variant could not be ruled out of causing disease. Due to the potential impact of frameshift variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance, but suspicious for pathogenicity for autosomal recessive spastic paraplegia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Labcorp Genetics |
RCV000779162 | SCV000963277 | pathogenic | Hereditary spastic paraplegia 11 | 2023-09-26 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asn1583*) in the SPG11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SPG11 are known to be pathogenic (PMID: 19105190, 20110243, 22154821, 26556829). This variant is present in population databases (rs764186203, gnomAD 0.002%). 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: 632235). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV003279056 | SCV003959171 | pathogenic | Inborn genetic diseases | 2023-05-12 | criteria provided, single submitter | clinical testing | The c.4746_4747insTG (p.N1583*) alteration, located in exon 28 (coding exon 28) of the SPG11 gene, consists of an insertion of TG at position 4746. This changes the amino acid from an asparagine (N) to a stop codon at amino acid position 1583. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from gnomAD, the TG allele has an overall frequency of 0.001% (2/251248) total alleles studied. The highest observed frequency was 0.002% (2/113550) of European (non-Finnish) alleles. Based on the available evidence, this alteration is classified as pathogenic. |
| Mayo Clinic Laboratories, |
RCV004792455 | SCV005414260 | likely pathogenic | not provided | 2023-06-14 | criteria provided, single submitter | clinical testing | PM2_moderate, PVS1 |