Total submissions: 18
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Biesecker Lab/Clinical Genomics Section, |
RCV000172728 | SCV000051506 | likely benign | not provided | 2013-06-24 | criteria provided, single submitter | research | |
Laboratory for Molecular Medicine, |
RCV000040454 | SCV000064145 | benign | not specified | 2018-06-14 | criteria provided, single submitter | clinical testing | The p.Ala1827Ser variant in TTN is classified as benign because it has been iden tified in 0.13% (165/126446) of European chromosomes by the Genome Aggregation D atabase (gnomAD, http://gnomad.broadinstitute.org/). ACMG/AMP Criteria applied: BA1. |
Eurofins Ntd Llc |
RCV000172728 | SCV000228655 | uncertain significance | not provided | 2018-07-02 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000172728 | SCV000238006 | likely benign | not provided | 2020-08-20 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 26272908, 24033266, 23861362, 24503780) |
Illumina Laboratory Services, |
RCV003329159 | SCV000424979 | uncertain significance | TTN-Related Disorders | 2023-05-02 | criteria provided, single submitter | clinical testing | The TTN c.5479G>T (p.Ala1827Ser) variant is a missense variant located in exon 28 of the meta isoform NM_001267550 between the Z-disk and the I-band, and more specifically between the Ig-like-8 and Ig-like-9 domains. The p.Ala1827Ser variant is reported at a frequency of 0.00150 in the European (non-Finnish) population of the Genome Aggregation Database (gnomAD) v3.1.1 and is therefore considered a likely benign variant for all dominantly inherited TTN-related disorders. No homozygous control individuals have been reported for this variant in gnomAD v2.1.1 and 3.1.1. To our knowledge, this variant has not been reported in any TTN-related myopathies with extra-cardiac features, and thus the possibility that this variant contributes to recessive myopathy when found in homozygous or compound-heterozygous state with another variant cannot be excluded at this time. Based on the available evidence, the p.Ala1827Ser is classified as a variant of uncertain significance for recessively inherited TTN-related myopathy. |
Invitae | RCV001086722 | SCV000555443 | likely benign | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000617741 | SCV000735079 | likely benign | Cardiovascular phenotype | 2019-11-21 | 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. |
Center for Advanced Laboratory Medicine, |
RCV000852935 | SCV000995680 | likely benign | Primary dilated cardiomyopathy; Heart failure | 2018-07-03 | criteria provided, single submitter | clinical testing | |
Athena Diagnostics Inc | RCV000172728 | SCV001146435 | likely benign | not provided | 2019-04-11 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000040454 | SCV001748670 | likely benign | not specified | 2021-06-21 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.5479G>T (p.Ala1827Ser) results in a conservative amino acid change located in the I-Band domain 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 0.00087 in 250448 control chromosomes, predominantly at a frequency of 0.0014 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 3.58 fold of the estimated maximal expected allele frequency for a pathogenic variant in TTN causing Dilated Cardiomyopathy phenotype (0.00039), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. c.5479G>T has been reported in the literature in individuals affected with Dilated Cardiomyopathy (Campuzano_2015, Mademont-Soler_2017, Pugh_2014). These reports do 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. Nine 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. Based on the evidence outlined above, the variant was classified as likely benign. |
Ce |
RCV000172728 | SCV001962339 | uncertain significance | not provided | 2021-12-01 | criteria provided, single submitter | clinical testing | |
CHEO Genetics Diagnostic Laboratory, |
RCV001798169 | SCV002042568 | benign | Cardiomyopathy | 2020-06-08 | criteria provided, single submitter | clinical testing | |
Genome |
RCV000329243 | SCV000607069 | not provided | Tibial muscular dystrophy | 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. | |
Diagnostic Laboratory, |
RCV000172728 | SCV001739818 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics, |
RCV000040454 | SCV001925160 | benign | not specified | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000172728 | SCV001927595 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000172728 | SCV001957409 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000172728 | SCV001969775 | likely benign | not provided | no assertion criteria provided | clinical testing |