Total submissions: 27
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Biesecker Lab/Clinical Genomics Section, |
RCV000082448 | SCV000051461 | likely benign | not provided | 2013-06-24 | criteria provided, single submitter | research | |
Laboratory for Molecular Medicine, |
RCV000040789 | SCV000064480 | likely benign | not specified | 2015-03-30 | criteria provided, single submitter | clinical testing | p.Pro28158Ser in exon 288 of TTN: This variant is not expected to have clinical significance because it has been identified in 0.5% (77/15570) of South Asian ch romosomes and 0.3% (199/65938) European chromosomes by the Exome Aggregation Con sortium (ExAC, http://exac.broadinstitute.org; dbSNP rs72648247). |
Gene |
RCV000082448 | SCV000237762 | benign | not provided | 2018-04-24 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 24503780) |
Ambry Genetics | RCV000247505 | SCV000317739 | benign | Cardiovascular phenotype | 2023-05-08 | criteria provided, single submitter | clinical testing | This alteration is classified as 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. |
Eurofins Ntd Llc |
RCV000040789 | SCV000333503 | likely benign | not specified | 2015-07-31 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000277773 | SCV000420859 | uncertain significance | Hypertrophic cardiomyopathy | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000330728 | SCV000420860 | uncertain significance | Dilated Cardiomyopathy, Dominant | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000387528 | SCV000420861 | uncertain significance | Limb-girdle muscular dystrophy, recessive | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000290790 | SCV000420862 | uncertain significance | Early-onset myopathy with fatal cardiomyopathy | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000348133 | SCV000420863 | uncertain significance | Tibial muscular dystrophy | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000380748 | SCV000420864 | uncertain significance | Myopathy, myofibrillar, 9, with early respiratory failure | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001083918 | SCV000555653 | benign | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2024-01-29 | criteria provided, single submitter | clinical testing | |
Center for Advanced Laboratory Medicine, |
RCV000852789 | SCV000995515 | likely benign | Supraventricular tachycardia | 2017-10-02 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000082448 | SCV001152662 | likely benign | not provided | 2024-08-01 | criteria provided, single submitter | clinical testing | TTN: BS2 |
Illumina Laboratory Services, |
RCV001132527 | SCV001292190 | 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, |
RCV001132528 | SCV001292192 | 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000040789 | SCV001362767 | benign | not specified | 2020-12-04 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.84472C>T (p.Pro28158Ser) results in a non-conservative amino acid change located in the A-band of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0027 in 245714 control chromosomes in the gnomAD database, including 3 homozygotes. The observed variant frequency is approximately 4 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 benign. Co-occurrences with a pathogenic variant has been reported (MYBPC3 c.3628-41_3628-17del25), providing supporting evidence for a benign role. Eight 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/likely benign n=6, VUS n=2). Based on the evidence outlined above, the variant was classified as benign. |
CHEO Genetics Diagnostic Laboratory, |
RCV001798198 | SCV002043060 | benign | Cardiomyopathy | 2019-10-28 | criteria provided, single submitter | clinical testing | |
Neuberg Centre For Genomic Medicine, |
RCV000290790 | SCV004175766 | likely benign | Early-onset myopathy with fatal cardiomyopathy | 2023-03-01 | criteria provided, single submitter | clinical testing | |
Molecular Genetics, |
RCV003993770 | SCV004812411 | likely benign | TTN-related myopathy | 2023-05-05 | criteria provided, single submitter | clinical testing | South Asian population allele frequency is 0.5% (rs72648247, 159/30150 alleles, 1 homozygote in gnomAD v2.1) with a null REVEL score. Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.6.1, this variant is classified as LIKELY BENIGN. Following criteria are met: BS1 |
Diagnostic Laboratory, |
RCV000082448 | SCV001744097 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics, |
RCV000040789 | SCV001922154 | benign | not specified | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000040789 | SCV001931831 | benign | not specified | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000040789 | SCV001954515 | benign | not specified | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000082448 | SCV001971338 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Practice for Gait Abnormalities, |
RCV002227930 | SCV002507269 | likely pathogenic | Tip-toe gait | flagged submission | clinical testing | Myopathy refers to diseases that affect skeletal Muscles. These diseases attack muscle fibers, making muscles weak. Inherited myopathies are often caused by inheriting an abnormal gene mutation from a parent that causes the disease. Symptoms of congenital myopathies usually start at birth or in early childhood, but may not appear until the teen years or even later in adulthood. Congenital myopathies are somewhat unique compared with other inherited myopathies, as weakness typically affects all muscles and is often not progressive. Symptoms are: Muscle weakness, most commonly of upper arms and shoulders and thighs, muscle cramps, stiffness and spasms, fatigue with exertion and lack of energy. Our patients all walk on tiptoe, so they show similar symptoms. When we genetically test them with our toe walking panel, we find that around 90 per cent of them have a genetic variant that explains their toe walking. These can be assigned, for example, to the area of myopathies (such as variants of the COL6A3 gene), the area of hereditary neuropathies (such as variants of the KMT2C gene) or the area of metabolic diseases (such as variants of the PYGM gene). In a smaller group of patients with almost identical symptoms, no abnormality is found in the genes of our panel, but spastic paraplegia can be detected. In another small group of our toe walkers, no abnormalities can be detected in the genes analysed in our toe walking panel, nor do they suffer from spastic paraplegia, as is also the case with healthy children. In contrast to these, however, they show a tiptoe gait. These patients suffer from infantile cerebral palsy, in which toe walking can also be observed. | |
Prevention |
RCV004534939 | SCV004754184 | likely benign | TTN-related disorder | 2019-06-13 | 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). |