Total submissions: 18
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Biesecker Lab/Clinical Genomics Section, |
RCV000172312 | SCV000054986 | uncertain significance | not provided | 2013-06-24 | criteria provided, single submitter | research | |
Gene |
RCV000172312 | SCV000237304 | likely benign | not provided | 2021-02-15 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 23861362, 32403337) |
Ambry Genetics | RCV000242658 | SCV000319109 | uncertain significance | Cardiovascular phenotype | 2013-10-07 | criteria provided, single submitter | clinical testing | The p.L15669P variant (also known as c.47006T>C) is located in coding exon 230 of theTTNgene. This alteration results from a T to C substitution at nucleotide position 47006. The leucine at codon 15669 is replaced by proline, an amino acid with some similar properties. This variant was previously reported in dbSNP asrs201412693. Based on data from the NHLBI Exome Sequencing Project (ESP), the C-allele has an overall frequency of approximately 0.07% (8/12090), having been observed in0.08% (7/8262)of European American alleles, and in 00.03% (1/3828)of African American alleles studied. This variant was not reported in the 1000 Genomes Project. Based on protein sequence alignment, this amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be benign and tolerated by PolyPhen and SIFT in silico analyses, respectively.Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |
Eurofins Ntd Llc |
RCV000172312 | SCV000332821 | uncertain significance | not provided | 2015-07-17 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000312071 | SCV000422786 | 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, |
RCV000366773 | SCV000422787 | 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, |
RCV000277068 | SCV000422788 | 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, |
RCV000313378 | SCV000422789 | 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. |
Illumina Laboratory Services, |
RCV000354316 | SCV000422790 | 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. |
Labcorp Genetics |
RCV001082395 | SCV000542513 | likely benign | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2024-01-20 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000259186 | SCV000710954 | uncertain significance | not specified | 2017-04-20 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The p.Leu15669Pro v ariant in TTN has not been previously reported in individuals with cardiomyopath y, but has been identified in 0.1% (141/126168) of European chromosomes by the g enome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org/; dbSNP rs2 01412693). This variant has been reported in ClinVar (Variation ID: 191944) as o f uncertain significance or likely benign. Leucine (Leu) at position 15669 is no t conserved in mammals or evolutionarily distant species, supporting that a chan ge at this position may be tolerated. In summary, while the clinical significanc e of the p.Leu15669Pro variant is uncertain, these data suggest that it is more likely to be benign. |
CHEO Genetics Diagnostic Laboratory, |
RCV000768993 | SCV000900366 | benign | Cardiomyopathy | 2022-03-18 | criteria provided, single submitter | clinical testing | |
Center for Advanced Laboratory Medicine, |
RCV000395819 | SCV000995571 | likely benign | Hypertrophic cardiomyopathy | 2019-04-01 | criteria provided, single submitter | clinical testing | |
Athena Diagnostics | RCV000259186 | SCV001879665 | benign | not specified | 2021-02-09 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000172312 | SCV003823571 | uncertain significance | not provided | 2022-05-13 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000172312 | SCV004011267 | likely benign | not provided | 2024-01-01 | criteria provided, single submitter | clinical testing | TTN: BP4, BS1 |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000259186 | SCV004100177 | likely benign | not specified | 2023-09-03 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV004535173 | SCV004119938 | uncertain significance | TTN-related disorder | 2022-10-26 | criteria provided, single submitter | clinical testing | The TTN c.54710T>C variant is predicted to result in the amino acid substitution p.Leu18237Pro. This variant was reported, along with a second TTN missense variant, in an individual with muscle weakness and asymmetric extensor finger (Patient #43 in Supplementary data, Gonzalez-Quereda et al. 2020. PubMed ID: 32403337). This variant was also reported, along with a de novo multi-exon TTN deletion, in an individual with skeletal myopathy, facial weakness, and dilated cardiomyopathy (Roggenbuck et al. 2019. PubMed ID: 31489791). This variant was also documented in an individual with cardiomyopathy; however, this individual also harbored compound heterozygous truncating variants in TTN (Patient #29 in Table S3, Rees et al. 2021. PubMed ID: 33449170). This variant is reported in 0.11% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-179468704-A-G). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |