Total submissions: 22
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Biesecker Lab/Clinical Genomics Section, |
RCV000040588 | SCV000051708 | benign | not specified | 2013-06-24 | criteria provided, single submitter | research | |
Laboratory for Molecular Medicine, |
RCV000040588 | SCV000064279 | benign | not specified | 2015-03-30 | criteria provided, single submitter | clinical testing | p.Thr21743Ala in exon 275 of TTN: This variant is not expected to have clinical significance because it has been identified in 0.9% (60/6610) of Finnish chromos omes and 0.7% (477/65890) European chromosomes, including two homozygous individ uals, by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs56201325). |
Genetic Services Laboratory, |
RCV000118779 | SCV000153340 | likely benign | not provided | 2015-02-10 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000040588 | SCV000237520 | benign | not specified | 2016-11-28 | 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. |
Ambry Genetics | RCV000249950 | SCV000318899 | benign | Cardiovascular phenotype | 2020-07-29 | criteria provided, single submitter | clinical testing | General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance |
Eurofins Ntd Llc |
RCV000040588 | SCV000332032 | likely benign | not specified | 2015-06-10 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001083516 | SCV000555077 | benign | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Athena Diagnostics Inc | RCV000040588 | SCV000616138 | benign | not specified | 2021-04-01 | criteria provided, single submitter | clinical testing | |
CHEO Genetics Diagnostic Laboratory, |
RCV000769952 | SCV000901378 | benign | Cardiomyopathy | 2018-01-29 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000118779 | SCV001152756 | likely benign | not provided | 2023-09-01 | criteria provided, single submitter | clinical testing | TTN: BP4, BS2 |
ARUP Laboratories, |
RCV000040588 | SCV001159345 | uncertain significance | not specified | 2018-11-24 | criteria provided, single submitter | clinical testing | The TTN c.65227A>G; p.Thr21743Ala variant (rs56201325; ClinVar Variation ID: 47318) 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.Thr21743Ala 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. |
Illumina Laboratory Services, |
RCV001131595 | SCV001291226 | 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, |
RCV001131996 | SCV001291647 | likely benign | 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. |
Illumina Laboratory Services, |
RCV001131997 | SCV001291648 | 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. |
Illumina Laboratory Services, |
RCV001131998 | SCV001291649 | 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, |
RCV001131999 | SCV001291650 | 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000040588 | SCV001426966 | likely benign | not specified | 2020-07-06 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.65227A>G (p.Thr21743Ala) results in a non-conservative amino acid change located in the A-band region (cardiodb.org) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.004 in 244666 control chromosomes in the gnomAD database, including 3 homozygotes. The observed variant frequency is approximately 6.4- fold the estimated maximal expected allele frequency for a pathogenic variant in TTN causing Cardiomyopathy phenotype (0.00063), strongly suggesting that the variant is benign. c.65227A>G has been reported in the literature in individuals affected with Cardiomyopathy (examples- Lopes_2013, Pugh_2014, Campuzano_2015). 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. 13 clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (benign, n=7; likely benign, n=4; uncertain significance, n=2). Based on the evidence outlined above, the variant was classified as likely benign. |
Diagnostic Laboratory, |
RCV000118779 | SCV001739936 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000118779 | SCV001928511 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000040588 | SCV001957147 | benign | not specified | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000040588 | SCV001971750 | benign | not specified | no assertion criteria provided | clinical testing | ||
Clinical Genetics, |
RCV000040588 | SCV001979057 | benign | not specified | no assertion criteria provided | clinical testing |