Total submissions: 21
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Biesecker Lab/Clinical Genomics Section, |
RCV000172694 | SCV000051449 | likely benign | not provided | 2013-06-24 | criteria provided, single submitter | research | |
Laboratory for Molecular Medicine, |
RCV000039941 | SCV000063632 | uncertain significance | not specified | 2014-09-19 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The p.Glu5537Lys va riant in TTN has been identified by our laboratory in 1 Caucasian adult with HCM who also carried a likely disease-causing variant in another gene, 1 adult of u nspecified ethnicity with DCM, and 1 African American infant with severe RVH. Th is variant has also been identified in 0.1% (12/8216) of European American chrom osomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/, Ng 2013; dbSNP rs72648958). Computational prediction tools and conservation ana lysis do not provide strong support for or against an impact to the protein. In summary, while the clinical significance of the p.Glu5537Lys variant is uncertai n, its presence in various cardiomyopathies with different mechanisms of disease and its frequency in controls suggests that it is more likely to be benign. |
Gene |
RCV000172694 | SCV000238282 | likely benign | not provided | 2020-09-23 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 23396983, 23861362) |
Labcorp Genetics |
RCV001079880 | SCV000286491 | likely benign | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2024-01-25 | criteria provided, single submitter | clinical testing | |
Eurofins Ntd Llc |
RCV000172694 | SCV000333068 | uncertain significance | not provided | 2018-08-30 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV000039941 | SCV000597705 | uncertain significance | not specified | 2016-09-20 | criteria provided, single submitter | clinical testing | |
Athena Diagnostics | RCV000039941 | SCV000616018 | benign | not specified | 2024-07-30 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000172694 | SCV001153057 | likely benign | not provided | 2024-11-01 | criteria provided, single submitter | clinical testing | TTN: BS2 |
Illumina Laboratory Services, |
RCV001131917 | SCV001291561 | benign | Tibial muscular dystrophy | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. |
Illumina Laboratory Services, |
RCV001131918 | SCV001291562 | uncertain significance | Dilated cardiomyopathy 1G | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Illumina Laboratory Services, |
RCV001131919 | SCV001291563 | uncertain significance | Early-onset myopathy with fatal cardiomyopathy | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Illumina Laboratory Services, |
RCV001132883 | SCV001292562 | benign | Myopathy, myofibrillar, 9, with early respiratory failure | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. |
Illumina Laboratory Services, |
RCV001132884 | SCV001292563 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2J | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000039941 | SCV001337973 | likely benign | not specified | 2021-04-26 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.16609G>A (p.Glu5537Lys) results in a conservative amino acid change located in the I-Band region 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 0.001 in 245308 control chromosomes, predominantly at a frequency of 0.0017 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 3 fold of the estimated maximal expected allele frequency for a pathogenic variant in TTN causing Cardiomyopathy phenotype (0.00063), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. c.16609G>A has been reported in the literature in individuals affected with Cardiomyopathy (Campuzano_2015, Mademont-Soler_2017, Mates_2018). These reports do not provide unequivocal conclusions about association of the variant with Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Nine ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (n=5), likely benign (n=2) and benign (n=2). Based on the evidence outlined above, the variant was classified as likely benign. |
Baylor Genetics | RCV001132883 | SCV001528488 | uncertain significance | Myopathy, myofibrillar, 9, with early respiratory failure | 2018-01-18 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
Mayo Clinic Laboratories, |
RCV000172694 | SCV001713251 | uncertain significance | not provided | 2023-01-16 | criteria provided, single submitter | clinical testing | |
CHEO Genetics Diagnostic Laboratory, |
RCV001798134 | SCV002042394 | benign | Cardiomyopathy | 2019-07-09 | criteria provided, single submitter | clinical testing | |
Diagnostic Laboratory, |
RCV000172694 | SCV001740088 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics, |
RCV000039941 | SCV001925984 | benign | not specified | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000172694 | SCV001970848 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Prevention |
RCV004534864 | SCV004752316 | likely benign | TTN-related disorder | 2022-08-11 | no assertion criteria provided | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |