Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics | RCV001644611 | SCV000614947 | benign | not specified | 2021-02-26 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001081341 | SCV001004581 | likely benign | Spastic paraplegia | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV001109615 | SCV001266969 | uncertain significance | Charlevoix-Saguenay spastic ataxia | 2018-01-13 | 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. |
Genome- |
RCV001109615 | SCV002026663 | likely benign | Charlevoix-Saguenay spastic ataxia | 2021-09-05 | criteria provided, single submitter | clinical testing | |
Genome Diagnostics Laboratory, |
RCV001848892 | SCV002105023 | uncertain significance | Hereditary spastic paraplegia | 2017-05-29 | criteria provided, single submitter | clinical testing | |
MGZ Medical Genetics Center | RCV001109615 | SCV002580702 | uncertain significance | Charlevoix-Saguenay spastic ataxia | 2022-02-26 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV000516574 | SCV004226412 | uncertain significance | not provided | 2022-09-14 | criteria provided, single submitter | clinical testing | BS1 |
Department of Pathology and Laboratory Medicine, |
RCV000516574 | SCV001549454 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The SACS p.Arg976Ser variant was not identified in the literature nor was it identified in Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs139993038) and ClinVar (classified as a VUS by Athena Diagnostics Inc). The variant was also identified in control databases in 110 of 282716 chromosomes at a frequency of 0.000389 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 105 of 24960 chromosomes (freq: 0.004207), Latino in 4 of 35424 chromosomes (freq: 0.000113) and European (non-Finnish) in 1 of 129084 chromosomes (freq: 0.000008), while the variant was not observed in the Ashkenazi Jewish, East Asian, European (Finnish), Other, and South Asian populations. The p.Arg976 residue is conserved across mammals and other organisms, and four out of five computational analyses (PolyPhen-2, SIFT, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. | |
Prevention |
RCV003905307 | SCV004724631 | likely benign | SACS-related disorder | 2022-06-27 | no assertion criteria provided | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |