Total submissions: 14
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000040663 | SCV000064354 | uncertain significance | not specified | 2013-07-05 | criteria provided, single submitter | clinical testing | The Glu24427Lys variant in TTN has been identified by our laboratory in 1 Caucas ian individual with DCM (LMM unpublished data) and was not identified in large p opulation studies. Glutamic acid (Glu) at position 24427 is not well conserved i n evolution and 1 species (zebra finch) carries a lysine (Lys; this variant) at this position, raising the possibility that this change may be tolerated. Other computational analyses (biochemical amino acid properties, AlignGVGD, PolyPhen, and SIFT) do not provide strong support for or against an impact to the protein. At this time, additional information is needed to fully assess the clinical sig nificance of this variant. |
Gene |
RCV000726121 | SCV000237607 | likely benign | not provided | 2021-03-31 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 24503780) |
Eurofins Ntd Llc |
RCV000726121 | SCV000342142 | uncertain significance | not provided | 2016-08-25 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001079917 | SCV000643741 | likely benign | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2023-12-24 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000617992 | SCV000737292 | uncertain significance | Cardiovascular phenotype | 2017-07-12 | criteria provided, single submitter | clinical testing | The p.E17930K variant (also known as c.53788G>A), located in coding exon 153 of the TTN gene, results from a G to A substitution at nucleotide position 53788. The glutamic acid at codon 17930 is replaced by lysine, an amino acid with similar properties. This alteration was reported in an individual with features of dilated cardiomyopathy (DCM) who also had additional alterations in TTN and other cardiac-related genes (Pugh TJ et al. Genet. Med. 2014;16:601-8). This amino acid position is not well conserved in available vertebrate species, and lysine is the reference amino acid in other 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 alteration remains unclear. |
ARUP Laboratories, |
RCV000726121 | SCV001160503 | uncertain significance | not provided | 2023-11-01 | criteria provided, single submitter | clinical testing | The TTN c.80983G>A; p.Glu26995Lys variant (rs397517719; ClinVar Variation ID: 47393) is rare in the general population (<0.2% allele frequency in the Genome Aggregation Database) and has been reported in one individual with dilated cardiomyopathy (DCM) (Pugh 2014). The clinical relevance of rare missense variants in this gene, which are identified on average once per individual sequenced in affected populations (Herman 2012), is not well understood. Yet, evidence suggests that the vast majority of such missense variants do not contribute to the clinical outcome of DCM (Begay 2015). Thus, the clinical significance of the p.Glu26995Lys variant cannot be determined with certainty. References: Begay RL et al. Role of Titin Missense Variants in Dilated Cardiomyopathy. J Am Heart Assoc. 2015 Nov 13;4(11). Herman DS et al. Truncations of titin causing dilated cardiomyopathy. N Engl J Med. 2012 Feb 16;366(7):619-28. Linke WA and Hamdani N. Gigantic business: titin properties and function through thick and thin. Circ Res 2014; 114(6): 1052-1068. Pugh TJ et al. The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing. Genet Med. 2014 Aug;16(8):601-8. PMID: 24503780. |
Illumina Laboratory Services, |
RCV001132747 | SCV001292418 | 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, |
RCV001132748 | SCV001292419 | 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, |
RCV001132749 | SCV001292420 | 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, |
RCV001136159 | SCV001295981 | 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, |
RCV001136160 | SCV001295982 | 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. |
CHEO Genetics Diagnostic Laboratory, |
RCV001798182 | SCV002043001 | benign | Cardiomyopathy | 2021-05-05 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000726121 | SCV003824744 | uncertain significance | not provided | 2022-08-18 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV000726121 | SCV004225806 | uncertain significance | not provided | 2022-10-07 | criteria provided, single submitter | clinical testing | BP4 |