Total submissions: 15
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000727677 | SCV000237706 | likely benign | not provided | 2021-06-07 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 26582918) |
Laboratory for Molecular Medicine, |
RCV000223660 | SCV000272791 | uncertain significance | not specified | 2015-05-28 | criteria provided, single submitter | clinical testing | The p.Arg27006Cys variant in TTN has not been previously reported in individuals with cardiomyopathy, but has been identified in 16/66722 European chromosomes a nd 6/8590 East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http ://exac.broadinstitute.org; dbSNP rs200513274). Computational prediction tools a nd conservation analysis suggest that this variant may impact the protein, thoug h this information is not predictive enough to determine pathogenicity. In summa ry, the clinical significance of the p.Arg27006Cys variant is uncertain. |
Illumina Laboratory Services, |
RCV000404508 | SCV000421033 | 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, |
RCV000307858 | SCV000421034 | 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, |
RCV000396053 | SCV000421036 | 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, |
RCV000301842 | SCV000421037 | 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, |
RCV000359092 | SCV000421038 | 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. |
Labcorp Genetics |
RCV000526235 | SCV000643849 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2017-12-26 | criteria provided, single submitter | clinical testing | |
Eurofins Ntd Llc |
RCV000727677 | SCV000854990 | uncertain significance | not provided | 2018-07-23 | criteria provided, single submitter | clinical testing | |
Athena Diagnostics | RCV000727677 | SCV001475046 | likely benign | not provided | 2020-06-08 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000223660 | SCV002500567 | uncertain significance | not specified | 2023-01-23 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.81016C>T (p.Arg27006Cys) 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 0.00025 in 248676 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in TTN causing Dilated Cardiomyopathy (0.00025 vs 0.00039), allowing no conclusion about variant significance. c.81016C>T has been reported in the literature in an individual with suspected sudden cardiac death (Hertz_2016). This report does 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. Eight ClinVar submitters (evaluation after 2014) cite this variant as uncertain significance (n=5), likely benign (n=2) and benign (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance. |
Ambry Genetics | RCV002354516 | SCV002660300 | uncertain significance | Cardiovascular phenotype | 2020-02-13 | criteria provided, single submitter | clinical testing | The p.R20509C variant (also known as c.61525C>T), located in coding exon 159 of the TTN gene, results from a C to T substitution at nucleotide position 61525. The arginine at codon 20509 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Revvity Omics, |
RCV000727677 | SCV003821042 | uncertain significance | not provided | 2023-06-02 | criteria provided, single submitter | clinical testing | |
Genome |
RCV000509283 | SCV000607145 | not provided | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J; Tibial muscular dystrophy; Myopathy, myofibrillar, 9, with early respiratory failure; Hypertrophic cardiomyopathy 9 | no assertion provided | phenotyping only | GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. | |
Prevention |
RCV004537558 | SCV004731706 | uncertain significance | TTN-related disorder | 2023-12-09 | no assertion criteria provided | clinical testing | The TTN c.88720C>T variant is predicted to result in the amino acid substitution p.Arg29574Cys. This variant has been reported in an individual with a cardiac phenotype who was also positive for a second missense variant in TTN (Case 32, Table S1, Hertz et al. 2015. PubMed ID: 26383259). This variant is reported in 0.041% of alleles in individuals of East Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |