Total submissions: 21
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Biesecker Lab/Clinical Genomics Section, |
RCV000172664 | SCV000051299 | likely benign | not provided | 2013-06-24 | criteria provided, single submitter | research | |
Laboratory for Molecular Medicine, |
RCV000152339 | SCV000201237 | uncertain significance | not specified | 2014-06-18 | criteria provided, single submitter | clinical testing | The Arg14337His variant in TTN has not been previously reported in individuals w ith cardiomyopathy, but has been identified in 5/8286 European American chromoso mes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; db SNP rs191539637). Computational prediction tools and conservation analysis sugge st that this variant may impact the protein, though this information is not pred ictive enough to determine pathogenicity. In summary, the clinical significance of the Arg14337His variant is uncertain. |
Gene |
RCV000152339 | SCV000237259 | likely benign | not specified | 2017-11-07 | 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 | RCV001086129 | SCV000261959 | likely benign | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2024-01-22 | criteria provided, single submitter | clinical testing | |
Eurofins Ntd Llc |
RCV000172664 | SCV000339544 | uncertain significance | not provided | 2016-02-09 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000276790 | SCV000422977 | uncertain significance | 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, 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, |
RCV000331815 | SCV000422978 | uncertain significance | 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, 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, |
RCV000367766 | SCV000422979 | 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, |
RCV000328242 | SCV000422981 | 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. |
Illumina Laboratory Services, |
RCV000382730 | SCV000422982 | 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. |
Ambry Genetics | RCV000622012 | SCV000735866 | likely benign | Cardiovascular phenotype | 2018-11-23 | 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. |
ARUP Laboratories, |
RCV000172664 | SCV000884782 | uncertain significance | not provided | 2019-12-28 | criteria provided, single submitter | clinical testing | The TTN c.50714G>A; p.Arg16905His variant (rs191539637; ClinVar Variation ID: 166005) is rare in the general population (<1% allele frequency in the Genome Aggregation Database) and has not been reported in the medical literature in association with dilated cardiomyopathy (DCM) or other TTN-related disease. The clinical relevance of rare missense variants in this gene, which are identified on average once per individual sequenced in affected populations (Herman 2012), is not well understood. Yet, evidence suggests that the vast majority of such missense variants do not contribute to the clinical outcome of DCM (Begay 2015). Thus, the clinical significance of the p.Arg16905His variant cannot be determined with certainty. References: Begay RL et al. Role of Titin Missense Variants in Dilated Cardiomyopathy. J Am Heart Assoc. 2015 Nov 13;4(11). Herman DS et al. Truncations of titin causing dilated cardiomyopathy. N Engl J Med. 2012 Feb 16;366(7):619-28. Linke and Hamdani. Gigantic business: titin properties and function through thick and thin. Circ Res 2014; 114(6): 1052-1068. |
Ce |
RCV000172664 | SCV000892601 | uncertain significance | not provided | 2018-04-01 | criteria provided, single submitter | clinical testing | |
Athena Diagnostics Inc | RCV000152339 | SCV001475007 | benign | not specified | 2019-11-05 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000172664 | SCV003819705 | uncertain significance | not provided | 2023-03-29 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000152339 | SCV003844822 | uncertain significance | not specified | 2023-02-15 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.43010G>A (p.Arg14337His) results in a non-conservative amino acid change located in the A band of the encoded protein sequence. Three of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00039 in 247328 control chromosomes (gnomAD). This frequency is similar to the estimated frequency for a pathogenic variant in TTN causing Dilated Cardiomyopathy (0.00039 vs 0.00039), suggesting a benign role for this variant. To our knowledge, no occurrence of c.43010G>A in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Ten clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely pathogenic (n=1), VUS (n=4) and likely benign (n=5). Based on the evidence outlined above, the variant was classified as uncertain significance. |
Clinical Genetics, |
RCV000172664 | SCV001921128 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000172664 | SCV001928957 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000172664 | SCV001960115 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000172664 | SCV001976128 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Practice for Gait Abnormalities, |
RCV001837462 | SCV002098341 | likely pathogenic | Tip-toe gait | 2022-01-11 | flagged submission | clinical testing |