Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000154694 | SCV000204373 | uncertain significance | not specified | 2013-04-12 | criteria provided, single submitter | clinical testing | The Pro39Leu variant in CRYAB has not been reported in individuals with cardiomy opathy, but has been identified in 5/8594 European American chromosomes by the N HLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs1497872 33). Computational analyses (biochemical amino acid properties, conservation, Al ignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an im pact to the protein. Additional information is needed to fully assess the clinic al significance of this variant. |
Illumina Laboratory Services, |
RCV000335745 | SCV000367274 | uncertain significance | Fatal infantile hypertonic myofibrillar myopathy | 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, |
RCV000371984 | SCV000367275 | benign | Myofibrillar myopathy 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 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, |
RCV000296232 | SCV000367276 | benign | Cataract 16 multiple types | 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. |
Genetic Services Laboratory, |
RCV000154694 | SCV000594225 | uncertain significance | not specified | 2016-07-01 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000617272 | SCV000735832 | likely benign | Cardiovascular phenotype | 2023-12-27 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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 | RCV000655018 | SCV000776938 | uncertain significance | Dilated cardiomyopathy 1II | 2022-10-27 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 39 of the CRYAB protein (p.Pro39Leu). This variant is present in population databases (rs149787233, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with CRYAB-related conditions. ClinVar contains an entry for this variant (Variation ID: 178013). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |
Gene |
RCV001550214 | SCV001770510 | uncertain significance | not provided | 2023-03-10 | criteria provided, single submitter | clinical testing | Previously reported in an individual with left ventricular non-compaction who also harbored variants in the LMNA and MYLK2 genes (Miszalski-Jamka et al., 2017); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28798025, 32420686) |
Revvity Omics, |
RCV001550214 | SCV003828660 | uncertain significance | not provided | 2023-05-23 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV001550214 | SCV004226248 | uncertain significance | not provided | 2023-03-21 | criteria provided, single submitter | clinical testing | |
Zotz- |
RCV000655018 | SCV004099328 | uncertain significance | Dilated cardiomyopathy 1II | 2023-10-30 | no assertion criteria provided | clinical testing |