Total submissions: 15
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Biesecker Lab/Clinical Genomics Section, |
RCV000172366 | SCV000055035 | uncertain significance | not provided | 2013-06-24 | criteria provided, single submitter | research | |
Laboratory for Molecular Medicine, |
RCV000222100 | SCV000272622 | uncertain significance | not specified | 2015-06-25 | criteria provided, single submitter | clinical testing | The p.Lys9335Gln variant in TTN has not been previously reported in individuals with cardiomyopathy, but has been identified in 7/8600 East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP r s376287951). Computational prediction tools and conservation analysis do not pro vide strong support for or against an impact to the protein. In summary, the cli nical significance of the p.Lys9335Gln variant is uncertain. |
Labcorp Genetics |
RCV000548036 | SCV000642972 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2017-04-20 | criteria provided, single submitter | clinical testing | |
Eurofins Ntd Llc |
RCV000172366 | SCV000705228 | uncertain significance | not provided | 2017-01-11 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV001132692 | SCV001292360 | 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, |
RCV001132693 | SCV001292361 | 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, |
RCV001132694 | SCV001292362 | 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, |
RCV001132695 | SCV001292363 | 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. |
Illumina Laboratory Services, |
RCV001132696 | SCV001292364 | 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. |
Prevention |
RCV004535175 | SCV004120733 | uncertain significance | TTN-related disorder | 2022-09-28 | criteria provided, single submitter | clinical testing | The TTN c.31735A>C variant is predicted to result in the amino acid substitution p.Lys10579Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.087% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-179556770-T-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000222100 | SCV004223688 | uncertain significance | not specified | 2023-11-10 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.28003A>C (p.Lys9335Gln) results in a conservative amino acid change located in the I-band region of the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8e-05 in 248950 control chromosomes. To our knowledge, no occurrence of c.28003A>C in individuals affected with Limb-Girdle Muscular Dystrophy, Type 2J, or other TTN-related diseases and no experimental evidence demonstrating its impact on protein function have been reported. Five submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 (VUS, n=4; Benign, n=1). Based on the evidence outlined above, the variant was classified as uncertain significance. |
Revvity Omics, |
RCV000172366 | SCV004237394 | uncertain significance | not provided | 2023-05-19 | criteria provided, single submitter | clinical testing | |
Victorian Clinical Genetics Services, |
RCV001132692 | SCV005398448 | uncertain significance | Dilated cardiomyopathy 1G | 2019-08-28 | criteria provided, single submitter | clinical testing | A heterozygous missense variant was identified, NM_001267550.1(TTN):c.31735A>C in exon 121 of 363 of the TTN gene. (NB: This variant is non-coding in NM_003319.4.) This substitution is predicted to create a minor amino acid change from lysine to glutamine at position 10579 of the protein, NP_001254479.1(TTN):p.(Lys10579Gln). The lysine at this position has moderate conservation (100 vertebrates, UCSC), and is located within the PEVK 2 repeat region. In silico software predictions of the pathogenicity of this variant are conflicting (Polyphen, CADD, Mutation Taster). The variant is present in the gnomAD population database at frequencies of 0.09% (17 heterozygotes, 0 homozygotes) and 0.008% (23 heterozygotes, 0 homozygotes) in the East Asian subpopulation and the global population, respectively. It has been previously reported as a VUS in clinical cases (ClinVar, LOVD). Based on information available at the time of curation, this variant has been classified as a VARIANT of UNCERTAIN SIGNIFICANCE (VUS). |
Clinical Genetics, |
RCV000172366 | SCV001919165 | uncertain significance | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000172366 | SCV001973677 | uncertain significance | not provided | no assertion criteria provided | clinical testing |