Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000517677 | SCV000236820 | likely pathogenic | not provided | 2022-12-18 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene or region of a gene for which loss of function is not a well-established mechanism of disease; Located in a region of TTN within the I-band in which the majority of loss of function variants are significantly associated with autosomal dominant titinopathies (Deo et al., 2016; Schafer et al., 2017); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27625338, 27869827) |
Genetic Services Laboratory, |
RCV000195104 | SCV000249248 | pathogenic | Myopathy | 2015-04-08 | criteria provided, single submitter | clinical testing | |
Athena Diagnostics Inc | RCV000517677 | SCV000616050 | likely pathogenic | not provided | 2016-08-30 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000778578 | SCV000914882 | uncertain significance | TTN-Related Disorders | 2018-11-14 | criteria provided, single submitter | clinical testing | The TTN c.25513C>T (p.Gln8505Ter) variant is a stop-gained variant, which was observed by ICSL 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 for this variant, it 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. No publications were found based on this search. Due to the potential impact of stop-gained variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for TTN-related disorders. |
Invitae | RCV001066897 | SCV001231920 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2023-08-10 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant is located in the I band of TTN (PMID: 25589632). Truncating variants in this region have been shown to be highly prevalent in the general population and unaffected individuals (PMID: 26701604, 22335739). However, truncating variants in this region have also been reported in individuals affected with autosomal recessive centronuclear myopathy (PMID: 23975875). ClinVar contains an entry for this variant (Variation ID: 202356). This premature translational stop signal has been observed in individual(s) with clinical features of TTN-related conditions (Invitae). This variant is present in population databases (rs746721983, gnomAD 0.07%). This sequence change creates a premature translational stop signal (p.Gln9749*) in the TTN gene. While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein. |
Revvity Omics, |
RCV000517677 | SCV003819068 | uncertain significance | not provided | 2019-08-01 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000517677 | SCV004704199 | uncertain significance | not provided | 2024-02-01 | criteria provided, single submitter | clinical testing |