Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Biesecker Lab/Clinical Genomics Section, |
RCV000172306 | SCV000054982 | uncertain significance | not provided | 2013-06-24 | criteria provided, single submitter | research | |
Ambry Genetics | RCV000246388 | SCV000319631 | uncertain significance | Cardiovascular phenotype | 2018-03-28 | criteria provided, single submitter | clinical testing | The p.P9687L variant (also known as c.29060C>T), located in coding exon 116 of the TTN gene, results from a C to T substitution at nucleotide position 29060. The proline at codon 9687 is replaced by leucine, an amino acid with similar properties. This alteration has been reported as p.P16184L (c.48551C>T) as a secondary cardiac variant in an exome cohort using the NM_133378.4 isoform (Ng D et al. Circ Cardiovasc Genet. 2013;6(4):337-46). This alteration was also reported in a subject with dilated cardiomyopathy (DCM) who also had variants in other cardiac-related genes (Forleo C et al. PLoS ONE, 2017 Jul;12:e0181842). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |
Genetic Services Laboratory, |
RCV000500554 | SCV000597693 | uncertain significance | not specified | 2016-03-04 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000643101 | SCV000764788 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2018-01-02 | criteria provided, single submitter | clinical testing | |
Athena Diagnostics | RCV000172306 | SCV000844720 | uncertain significance | not provided | 2017-08-28 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000764325 | SCV000895344 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J; Tibial muscular dystrophy; Myopathy, myofibrillar, 9, with early respiratory failure; Early-onset myopathy with fatal cardiomyopathy; Hypertrophic cardiomyopathy 9 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000172306 | SCV001152863 | uncertain significance | not provided | 2024-02-01 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000172306 | SCV001801756 | likely benign | not provided | 2022-05-10 | criteria provided, single submitter | clinical testing | See Variant Classification Assertion Criteria. |
Revvity Omics, |
RCV000172306 | SCV003822341 | uncertain significance | not provided | 2021-10-27 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000500554 | SCV004020328 | uncertain significance | not specified | 2023-06-26 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.48551C>T (p.Pro16184Leu) results in a non-conservative amino acid change located in the A-band of the encoded protein sequence. Two of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00017 in 247942 control chromosomes (gnomAD). c.48551C>T has been reported in the literature in individuals affected with dilated cardiomyopathy or sudden unexplained death without strong evidence of causality (Mates_2018, Campuzano_2015, Forleo_2017). These reports do not provide unequivocal conclusions about association of the variant with Limb-Girdle Muscular Dystrophy, Type 2J. The following publications have been ascertained in the context of this evaluation (PMID: 29511324, 26516846, 28750076). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven submitters have cited clinical-significance assessments for this variant to ClinVar after 2014, and classified it as uncertain significance (n=6) or likely benign (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance. |
Mayo Clinic Laboratories, |
RCV000172306 | SCV004225855 | uncertain significance | not provided | 2022-06-21 | criteria provided, single submitter | clinical testing | BP4 |