Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002316749 | SCV000850446 | likely benign | Inborn genetic diseases | 2018-08-10 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Invitae | RCV003596541 | SCV000948318 | uncertain significance | Myoclonic-atonic epilepsy | 2023-12-23 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 6 of the SLC6A1 gene. It does not directly change the encoded amino acid sequence of the SLC6A1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs368174761, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SLC6A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 589519). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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. |
New York Genome Center | RCV003444662 | SCV001815769 | uncertain significance | Myoclonic-astatic epilepsy | 2020-10-23 | criteria provided, single submitter | clinical testing | The inherited c.582-3C>T (p.?) missense variant in exon intron 6 of 15 of SLC6A1 has not been reported in affected individuals in the available literature. This variant is present in gnomADv3 at a very low frequency (4/143334 alleles, allele frequency = 0.00002791; no homozygotes) indicating it is not a common benign variant in the populations represented in this database. In silico predictors suggest this variant is possibly damaging (TRAP; score: 0.194) and benign (SpliceAI; score: 0.1). Given the contradicting evidence regarding its pathogenicity, the c.582-3C>T (p.?)variant identified in the SLC6A1 gene is reported as a Variant of Uncertain Significance. |