Total submissions: 13
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000130870 | SCV000185771 | benign | Hereditary cancer-predisposing syndrome | 2022-09-30 | criteria provided, single submitter | clinical testing | This alteration is classified as 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 |
RCV001328509 | SCV000254688 | likely benign | Renal cell carcinoma | 2024-02-01 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000484898 | SCV000573280 | uncertain significance | not provided | 2024-09-23 | criteria provided, single submitter | clinical testing | In silico analysis indicates that this missense variant does not alter protein structure/function; Observed in individuals with colorectal cancer and mesothelioma (PMID: 21774103, 21970370); This variant is associated with the following publications: (PMID: 21970370, 18709663, 24465403, 21904579, 28166811, 25992381, 21774103, 30949922, 29641532, 28259294) |
Fulgent Genetics, |
RCV000515234 | SCV000611396 | uncertain significance | Osteofibrous dysplasia; Papillary renal cell carcinoma type 1; Hepatocellular carcinoma; Autosomal recessive nonsyndromic hearing loss 97 | 2017-05-23 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000199439 | SCV001137444 | uncertain significance | Papillary renal cell carcinoma type 1 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000199439 | SCV001323161 | benign | Papillary renal cell carcinoma type 1 | 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. |
Institute of Human Genetics, |
RCV001262296 | SCV001440110 | uncertain significance | Breast carcinoma | 2019-01-01 | criteria provided, single submitter | clinical testing | |
Institute for Clinical Genetics, |
RCV000484898 | SCV002011105 | uncertain significance | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000130870 | SCV002532161 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-15 | criteria provided, single submitter | curation | |
St. |
RCV000199439 | SCV003928042 | uncertain significance | Papillary renal cell carcinoma type 1 | 2023-11-28 | criteria provided, single submitter | clinical testing | The MET c.406G>A (p.Val136Ile) missense change a maximum founder subpopulation frequency of 0.076% and a maximum non-founder subpopulation frequency of 0.043% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL predicts a benign effect on protein function, but this prediction has not been confirmed by functional studies. This variant has not been reported in individuals with hereditary papillary renal cell carcinoma. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |
Center for Genomic Medicine, |
RCV003320572 | SCV004025152 | uncertain significance | not specified | 2024-07-31 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003320572 | SCV005203946 | likely benign | not specified | 2024-06-24 | criteria provided, single submitter | clinical testing | Variant summary: MET c.406G>A (p.Val136Ile) results in a conservative amino acid change located in the Sema domain (IPR001627) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00028 in 249054 control chromosomes, predominantly at a frequency of 0.00039 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 260 fold of the estimated maximal expected allele frequency for a pathogenic variant in MET causing Papillary Renal Cell Carcinoma phenotype (1.5e-06). To our knowledge, no occurrence of c.406G>A in individuals affected with Papillary Renal Cell Carcinoma and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 142059). Based on the evidence outlined above, the variant was classified as likely benign. |
Prevention |
RCV003415953 | SCV004113140 | likely benign | MET-related disorder | 2024-01-04 | 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). |