Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000393561 | SCV000477850 | uncertain significance | Amyotrophic lateral sclerosis type 4 | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Illumina Laboratory Services, |
RCV000304137 | SCV000477851 | uncertain significance | Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| ARUP Laboratories, |
RCV001810866 | SCV001471688 | uncertain significance | not provided | 2019-09-13 | criteria provided, single submitter | clinical testing | The SETX c.3200C>T; p.Thr1067Ile variant (rs374091487), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 365360). This variant is found in the non-Finnish European population with an overall allele frequency of 0.005% (6/128938 alleles) in the Genome Aggregation Database. The threonine at codon 1067 is weakly conserved, and computational analyses (SIFT: damaging, PolyPhen-2: benign) predict conflicting effects of this variant on protein structure/function. However, due to limited information, the clinical significance of the p.Thr1067Ile variant is uncertain at this time. |
| Gene |
RCV001810866 | SCV002552898 | uncertain significance | not provided | 2022-07-19 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV002323570 | SCV002609182 | uncertain significance | Inborn genetic diseases | 2021-05-25 | criteria provided, single submitter | clinical testing | The p.T1067I variant (also known as c.3200C>T), located in coding exon 8 of the SETX gene, results from a C to T substitution at nucleotide position 3200. The threonine at codon 1067 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and isoleucine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the supporting evidence, this variant is unlikely to be causative of autosomal dominant juvenile amyotrophic lateral sclerosis 4 (ALS4); however, its contribution to the development of autosomal recessive spinocerebellar ataxia with axonal neuropathy 2 (SCAN2) is uncertain. |
| Invitae | RCV002523743 | SCV002944647 | likely benign | Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 | 2023-09-06 | criteria provided, single submitter | clinical testing |