Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000322222 | SCV000343088 | uncertain significance | not provided | 2016-12-19 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000541902 | SCV000649131 | uncertain significance | Autosomal recessive ataxia, Beauce type; Emery-Dreifuss muscular dystrophy 4, autosomal dominant | 2022-09-07 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 7683 of the SYNE1 protein (p.Val7683Ile). This variant is present in population databases (rs150550013, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with SYNE1-related conditions. ClinVar contains an entry for this variant (Variation ID: 288855). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
ARUP Laboratories, |
RCV000322222 | SCV000884642 | uncertain significance | not provided | 2017-09-29 | criteria provided, single submitter | clinical testing | The p.Val7683Ile variant (rs150550013) has not been reported in the medical literature. The p.Val7683Ile variant is listed in the Genome Aggregation Database (gnomAD) browser with an overall allele frequency of 0.02% (identified in 56 out of 276,916 chromosomes), and is classified as a variant of uncertain significance in ClinVar (Variant ID: 288855). The valine at codon 7683 is weakly conserved considering 12 species (Alamut software v2.10.0), and computational analyses predict that this variant does not affect the structure/function of the SYNE1 protein (SIFT: tolerated, PolyPhen2: benign, MutationTaster: polymorphism). However, based on the available information, the clinical significance of the p.Val7683Ile variant cannot be determined with certainty. |
Ce |
RCV000322222 | SCV001154914 | uncertain significance | not provided | 2018-09-01 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV001157122 | SCV001318668 | benign | Emery-Dreifuss muscular dystrophy 4, autosomal dominant | 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, |
RCV001157123 | SCV001318669 | uncertain significance | Autosomal recessive ataxia, Beauce type | 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. |
Gene |
RCV000322222 | SCV002072760 | uncertain significance | not provided | 2021-07-30 | 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 | RCV002518059 | SCV003686940 | likely benign | Inborn genetic diseases | 2021-07-15 | 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. |
Preventiongenetics, |
RCV003401265 | SCV004103088 | uncertain significance | SYNE1-related condition | 2023-09-20 | criteria provided, single submitter | clinical testing | The SYNE1 c.23047G>A variant is predicted to result in the amino acid substitution p.Val7683Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.040% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-152510428-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Mayo Clinic Laboratories, |
RCV000322222 | SCV004223957 | uncertain significance | not provided | 2018-12-10 | criteria provided, single submitter | clinical testing | BP4_strong |