Total submissions: 15
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000040407 | SCV000064098 | benign | not specified | 2012-03-19 | criteria provided, single submitter | clinical testing | p.Glu16978Gln in Exon 247 of TTN: This variant is not expected to have clinical significance because it has been identified in 1.2% (36/2994) of African America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS;). |
Gene |
RCV000040407 | SCV000169306 | benign | not specified | 2014-04-20 | 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. |
Invitae | RCV000463384 | SCV000555392 | benign | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2024-01-29 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000620821 | SCV000736034 | benign | Cardiovascular phenotype | 2017-05-31 | 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. |
CHEO Genetics Diagnostic Laboratory, |
RCV000770002 | SCV000901428 | benign | Cardiomyopathy | 2017-08-04 | criteria provided, single submitter | clinical testing | |
Center for Advanced Laboratory Medicine, |
RCV000852834 | SCV000995564 | benign | Cardiomyopathy; Ventricular fibrillation | 2019-05-20 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV001129739 | SCV001289282 | likely benign | Early-onset myopathy with fatal cardiomyopathy | 2018-01-13 | 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. |
Illumina Laboratory Services, |
RCV001129740 | SCV001289283 | likely benign | Dilated cardiomyopathy 1G | 2018-01-13 | 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. |
Illumina Laboratory Services, |
RCV001129741 | SCV001289284 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2J | 2018-01-13 | 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, |
RCV001129742 | SCV001289285 | benign | Myopathy, myofibrillar, 9, with early respiratory failure | 2018-01-13 | 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, |
RCV001134735 | SCV001294490 | benign | Tibial muscular dystrophy | 2018-01-13 | 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000040407 | SCV001478612 | benign | not specified | 2021-01-28 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.50932G>C (p.Glu16978Gln) results in a conservative amino acid change located in the A-band domain of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00073 in 247926 control chromosomes, predominantly at a frequency of 0.01 within the African or African-American subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 26 fold of the estimated maximal expected allele frequency for a pathogenic variant in TTN causing Dilated Cardiomyopathy phenotype (0.00039), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no experimental evidence demonstrating its impact on protein function have been reported. Seven ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (n=1), likely benign (n=1) and benign (n=5). Based on the evidence outlined above, the variant was classified as benign. |
Diagnostic Laboratory, |
RCV000040407 | SCV001744624 | benign | not specified | no assertion criteria provided | clinical testing | ||
Clinical Genetics, |
RCV000040407 | SCV001922833 | benign | not specified | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000040407 | SCV001929165 | benign | not specified | no assertion criteria provided | clinical testing |