Total submissions: 21
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Biesecker Lab/Clinical Genomics Section, |
RCV000039983 | SCV000051624 | benign | not specified | 2013-06-24 | criteria provided, single submitter | research | |
Laboratory for Molecular Medicine, |
RCV000039983 | SCV000063674 | benign | not specified | 2015-03-04 | criteria provided, single submitter | clinical testing | p.Ser6482Leu in exon 77 of TTN: This variant is not expected to have clinical si gnificance because it has been identified in 3.1% (205/6544) of Finnish chromoso mes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; d bSNP dbSNP rs17452588). |
Gene |
RCV000039983 | SCV000238329 | benign | not specified | 2016-10-24 | 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 | RCV000755421 | SCV000286509 | benign | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000248207 | SCV000318853 | benign | Cardiovascular phenotype | 2013-07-31 | criteria provided, single submitter | clinical testing | This alteration is classified as 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. |
Eurofins Ntd Llc |
RCV000039983 | SCV000332857 | benign | not specified | 2015-07-21 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000331984 | SCV000424232 | likely benign | Early-onset myopathy with fatal cardiomyopathy | 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 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, |
RCV000372590 | SCV000424233 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2J | 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, |
RCV000278120 | SCV000424234 | benign | Tibial muscular dystrophy | 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, |
RCV000373899 | SCV000424236 | likely benign | Dilated cardiomyopathy 1G | 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 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, |
RCV000284280 | SCV000424237 | benign | Myopathy, myofibrillar, 9, with early respiratory failure | 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. |
ARUP Laboratories, |
RCV001529703 | SCV000605489 | benign | not provided | 2021-08-24 | criteria provided, single submitter | clinical testing | |
CHEO Genetics Diagnostic Laboratory, |
RCV000770071 | SCV000901497 | benign | Cardiomyopathy | 2018-06-25 | criteria provided, single submitter | clinical testing | |
Center for Advanced Laboratory Medicine, |
RCV000337890 | SCV000995628 | benign | Hypertrophic cardiomyopathy | 2019-01-31 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000039983 | SCV001432106 | benign | not specified | 2020-08-17 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.19445C>T (p.Ser6482Leu) results in a non-conservative amino acid change located in the I-band 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 0.0071 in 247748 control chromosomes in the gnomAD database, including 14 homozygotes. The observed variant frequency is approximately 18 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 benign. c.19445C>T has been reported in the literature (e.g. Pugh_2014). These reports however, do not provide unequivocal conclusions about association of the variant with Dilated Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Ten ClinVar submitters (evaluation after 2014) cite the variant as benign/likely benign (n=9) or uncertain significance (n=1). Based on the evidence outlined above, the variant was classified as benign. |
Ce |
RCV001529703 | SCV002544171 | likely benign | not provided | 2024-04-01 | criteria provided, single submitter | clinical testing | TTN: BP4, BS2 |
Diagnostic Laboratory, |
RCV001529703 | SCV001743613 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Laboratory of Diagnostic Genome Analysis, |
RCV001529703 | SCV001797860 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics, |
RCV000039983 | SCV001921973 | benign | not specified | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000039983 | SCV001957101 | benign | not specified | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000039983 | SCV001973076 | benign | not specified | no assertion criteria provided | clinical testing |