Total submissions: 16
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000118298 | SCV000152671 | uncertain significance | not provided | 2013-08-27 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000118298 | SCV000279167 | uncertain significance | not provided | 2018-09-19 | criteria provided, single submitter | clinical testing | The Y990C variant has been reported previously in two individuals with Rolandic epilepsy; however, additional information was not provided (Bobbili et al., 2018). The Y990C variant is observed in 35/6312 (0.6%) alleles from individuals of Ashkenazi Jewish background in large population cohorts (Lek et al., 2016). The Y990C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Prevention |
RCV000222414 | SCV000309310 | likely benign | not specified | criteria provided, single submitter | clinical testing | ||
Illumina Laboratory Services, |
RCV000391228 | SCV000418517 | likely benign | Small fiber neuropathy | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000366834 | SCV000418519 | benign | Primary erythromelalgia | 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. |
Illumina Laboratory Services, |
RCV000391236 | SCV000418520 | uncertain significance | Channelopathy-associated congenital insensitivity to pain, autosomal recessive | 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, |
RCV000313714 | SCV000418521 | benign | Paroxysmal extreme pain disorder | 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. |
Invitae | RCV001080160 | SCV000548364 | likely benign | Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with febrile seizures plus, type 7 | 2024-01-27 | criteria provided, single submitter | clinical testing | |
Eurofins Ntd Llc |
RCV000118298 | SCV000700613 | uncertain significance | not provided | 2016-11-03 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV000118298 | SCV001714618 | uncertain significance | not provided | 2020-10-12 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002433611 | SCV002752082 | likely benign | Inborn genetic diseases | 2019-09-29 | 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. |
Ce |
RCV000118298 | SCV004033781 | likely benign | not provided | 2023-12-01 | criteria provided, single submitter | clinical testing | SCN9A: BP4 |
Bioinformatics Core, |
RCV000655986 | SCV000588262 | pathogenic | Childhood epilepsy with centrotemporal spikes | 2017-01-01 | no assertion criteria provided | case-control | CAADphred>15 |
Department of Pathology and Laboratory Medicine, |
RCV000118298 | SCV001551045 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The SCN9A p.Tyr990Cys variant was identified in 3 of 3192 proband chromosomes (frequency: 0.00094; one compound heterozygote and two heterozygotes) from individuals with peripheral neuropathy (Wadhawan_2017_PMID_29264398; Eijkenboom_2018_PMID_30554136). The variant was identified in dbSNP (ID: rs199692186) and ClinVar (classified as likely benign by PreventionGenetics, Invitae and Illumina, and as uncertain significance by GeneDx, EGL Genetic Diagnostics and Genetic Services Laboratory, University of Chicago, and classified as pathogenic by Bioinformatics Core Luxembourg Center for Systems Biomedicine). The variant was identified in control databases in 143 of 236408 chromosomes at a frequency of 0.0006049 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: Ashkenazi Jewish in 35 of 6532 chromosomes (freq: 0.005358), Other in 7 of 5826 chromosomes (freq: 0.001202), European (non-Finnish) in 92 of 113582 chromosomes (freq: 0.00081), European (Finnish) in 5 of 22294 chromosomes (freq: 0.000224), African in 3 of 23534 chromosomes (freq: 0.000128) and South Asian in 1 of 20024 chromosomes (freq: 0.00005), but was not observed in the Latino or East Asian populations. The p.Tyr990 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of 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. | |
Clinical Genetics, |
RCV000118298 | SCV001920403 | uncertain significance | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000118298 | SCV001954100 | uncertain significance | not provided | no assertion criteria provided | clinical testing |