Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000492290 | SCV000580788 | likely benign | Hereditary cancer-predisposing syndrome | 2020-08-14 | 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. |
Labcorp Genetics |
RCV001079302 | SCV000629339 | benign | Retinoblastoma | 2024-02-01 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000601517 | SCV000714123 | likely benign | not specified | 2018-02-15 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Illumina Laboratory Services, |
RCV001079302 | SCV001271625 | likely benign | Retinoblastoma | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000601517 | SCV002050810 | likely benign | not specified | 2021-12-07 | criteria provided, single submitter | clinical testing | Variant summary: RB1 c.628G>T (p.Asp210Tyr) results in a non-conservative amino acid change located in the Retinoblastoma-associated protein, N-terminal domain (IPR024599) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00016 in 250442 control chromosomes, predominantly at a frequency of 0.0038 within the Ashkenazi Jewish subpopulation in the gnomAD database. The observed variant frequency within Ashkenazi Jewish control individuals in the gnomAD database is approximately 91-fold of the estimated maximal expected allele frequency for a pathogenic variant in RB1 causing Retinoblastoma phenotype (4.2e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Ashkenazi Jewish origin. c.628G>T has been reported in the literature as a secondary finding in a study of cancer susceptibility genes in individuals affected with atherosclerosis (Johnston_2012). This report does not provide conclusions about association of the variant with Retinoblastoma. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submitters have assessed the variant since 2014: three have classified the variant as likely benign and one as benign. Based on the evidence outlined above, the variant was classified as likely benign. |
Sema4, |
RCV000492290 | SCV002530861 | likely benign | Hereditary cancer-predisposing syndrome | 2021-12-14 | criteria provided, single submitter | curation | |
Ce |
RCV000034597 | SCV004133123 | uncertain significance | not provided | 2023-09-01 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV001079302 | SCV004357198 | benign | Retinoblastoma | 2022-04-26 | criteria provided, single submitter | clinical testing | |
Biesecker Lab/Clinical Genomics Section, |
RCV000034597 | SCV000043464 | variant of unknown significance | not provided | 2012-07-13 | no assertion criteria provided | research | Converted during submission to Uncertain significance. |