Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics | RCV000518213 | SCV000615209 | uncertain significance | not provided | 2019-08-08 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000524648 | SCV000645283 | likely benign | Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 | 2022-12-19 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV001814998 | SCV002061932 | uncertain significance | not specified | 2021-06-16 | criteria provided, single submitter | clinical testing | DNA sequence analysis of the SETX gene demonstrated a sequence change c.7139G>A, in exon 24 that results in an amino acid change, p.Arg2380Gln. This sequence change has been described in three non-Finnish European individuals only in the gnomAD population database (dbSNP rs145397619). This sequence change has been previously described in an individual with ataxia with oculomotor apraxia type 2 (AOA2) however a second variant was not identified (PMID: 19696032). Two other changes affecting the same amino acid residue (p.Arg2380Gly, p.Arg2380Trp) have been reported in the homozygous state in individuals with AOA2 (PMIDs: 19696032, 23111195). The p.Arg2380Gln change affects a highly conserved amino acid residue located in the helicase of the SETX protein and in a region where other pathogenic missense variants have been described. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Arg2380Gln substitution. Due to the lack of functional studies, the clinical significance of the p.Arg2380Gln change remains unknown at this time. |
Revvity Omics, |
RCV000518213 | SCV003827517 | uncertain significance | not provided | 2022-01-01 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003233692 | SCV003931877 | uncertain significance | Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 | 2023-02-08 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003233693 | SCV003931888 | uncertain significance | Amyotrophic lateral sclerosis type 4 | 2023-02-08 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000518213 | SCV005051115 | likely pathogenic | not provided | 2024-05-01 | criteria provided, single submitter | clinical testing | SETX: PM2, PM3, PM5 |
Prevention |
RCV004541620 | SCV004797213 | uncertain significance | SETX-related disorder | 2023-11-29 | no assertion criteria provided | clinical testing | The SETX c.7139G>A variant is predicted to result in the amino acid substitution p.Arg2380Gln. This variant was reported along with a SETX nonsense variant in two individuals from a family with spinocerebellar ataxia with axonal neuropathy (Family ATX-27, Baviera-Muñoz et al. 2022. PubMed ID: 36530930). This variant was also reported in the heterozygous state in an individual with spinocerebellar ataxia with axonal neuropathy; however, a second plausible causative variant was not identified (Anheim et al. 2009. PubMed ID: 19696032). This variant is reported in 0.0023% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Different nucleotide substitutions affecting the same amino acid (p.Arg2380Gly and p.Arg2380Trp) have been reported in the homozygous state in individuals with spinocerebellar ataxia with axonal neuropathy (Anheim et al. 2009. PubMed ID: 19696032; Hammer et al. 2012. PubMed ID: 23111195). At this time, the clinical significance of the c.7139G>A (p.Arg2380Gln) variant is uncertain due to the absence of conclusive functional and genetic evidence. |