Total submissions: 28
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Biesecker Lab/Clinical Genomics Section, |
RCV000118794 | SCV000051485 | likely benign | not provided | 2013-06-24 | criteria provided, single submitter | research | |
Laboratory for Molecular Medicine, |
RCV000040867 | SCV000064558 | likely benign | not specified | 2016-01-13 | criteria provided, single submitter | clinical testing | p.Ala30197Gly in exon 301 of TTN: This variant is not expected to have clinical significance because it has been identified in 0.4% (281/66708) of European chro mosomes and 0.4% (28/6614) of Finnish chromosomes by the Exome Aggregation Conso rtium (ExAC, http://exac.broadinstitute.org/; dbSNP rs72648273). |
Genetic Services Laboratory, |
RCV000118794 | SCV000153410 | likely benign | not provided | 2015-02-10 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000118794 | SCV000237852 | likely benign | not provided | 2022-04-25 | criteria provided, single submitter | clinical testing | See Variant Classification Assertion Criteria. |
Ambry Genetics | RCV000248345 | SCV000317871 | likely benign | Cardiovascular phenotype | 2013-11-01 | criteria provided, single submitter | clinical testing | This alteration is classified as likely 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 |
RCV000040867 | SCV000333885 | likely benign | not specified | 2015-08-06 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000260558 | SCV000420458 | 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, |
RCV000322722 | SCV000420459 | uncertain significance | 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, 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, |
RCV000361061 | SCV000420460 | 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, |
RCV000264048 | SCV000420461 | 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. |
Illumina Laboratory Services, |
RCV000321435 | SCV000420462 | uncertain significance | 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, 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. |
Invitae | RCV001079943 | SCV000555060 | likely benign | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2024-02-01 | criteria provided, single submitter | clinical testing | |
Center for Pediatric Genomic Medicine, |
RCV000118794 | SCV000610886 | likely benign | not provided | 2017-06-26 | criteria provided, single submitter | clinical testing | |
CHEO Genetics Diagnostic Laboratory, |
RCV000768847 | SCV000900220 | benign | Cardiomyopathy | 2020-03-20 | criteria provided, single submitter | clinical testing | |
Center for Advanced Laboratory Medicine, |
RCV000354955 | SCV000995507 | likely benign | Hypertrophic cardiomyopathy | 2017-03-27 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000118794 | SCV001152621 | likely benign | not provided | 2023-09-01 | criteria provided, single submitter | clinical testing | TTN: BS1 |
Genetics and Genomics Program, |
RCV000354955 | SCV001434036 | likely benign | Hypertrophic cardiomyopathy | criteria provided, single submitter | research | ||
ARUP Laboratories, |
RCV000118794 | SCV001474077 | likely benign | not provided | 2021-08-15 | criteria provided, single submitter | clinical testing | |
Athena Diagnostics Inc | RCV000040867 | SCV001475822 | benign | not specified | 2020-01-21 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000040867 | SCV002074270 | likely benign | not specified | 2022-01-14 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.90590C>G (p.Ala30197Gly) results in a non-conservative amino acid change located in the A-band region of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.003 in 248714 control chromosomes. The observed variant frequency is approximately 8 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. Although this variant has been reported as likely benign in the literature (example, Al-Shafai_2021), to our knowledge, no occurrence of c.90590C>G in individuals affected with Dilated Cardiomyopathy and/or other associated phenotypes such as Limb-Girdle Muscular Dystrophy, Type 2J and no experimental evidence demonstrating its impact on protein function have been reported. Multiple clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation with a predominant consensus as benign/lilely benign (n=11). Based on the evidence outlined above, the variant was classified as likely benign. |
Stanford Center for Inherited Cardiovascular Disease, |
RCV000118794 | SCV000924998 | uncertain significance | not provided | 2012-12-01 | no assertion criteria provided | provider interpretation | |
Diagnostic Laboratory, |
RCV000118794 | SCV001740018 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics, |
RCV000040867 | SCV001921874 | benign | not specified | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000118794 | SCV001930146 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000040867 | SCV001953516 | benign | not specified | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000118794 | SCV001965167 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Laboratory of Diagnostic Genome Analysis, |
RCV000118794 | SCV002036187 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Practice for Gait Abnormalities, |
RCV002222153 | SCV002499647 | likely pathogenic | Tip-toe gait | no assertion criteria provided | clinical testing |