ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.80858C>T (p.Thr26953Met) (rs377506142)

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000172245 SCV000054926 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000155780 SCV000205491 uncertain significance not specified 2014-08-27 criteria provided, single submitter clinical testing The Thr24385Met variant in TTN has previously been identified by our laboratory in 1 adult with HCM, and was absent from large population studies. Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein, though 1 mammal (pika) carries a methionine ( Met; this variant) at this position, raising the possibility that this change ma y be tolerated. In summary, the clinical significance of the Thr24385Met variant is uncertain.
GeneDx RCV000172245 SCV000237605 benign not provided 2021-02-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV000254311 SCV000319143 uncertain significance Cardiovascular phenotype 2013-11-20 criteria provided, single submitter clinical testing The p.T24385M variant (also known as c.73154C>T) is located in coding exon 274 of the TTN gene. This alteration results from a C to T substitution at nucleotide position 73154. The threonine at codon 24385 is replaced by methionine, an amino acid with some similar properties. This variant was not reported in population-based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), the 1000 Genomes Project and the NHLBI Exome Sequencing Project (ESP). In the ESP, this variant was not reported in 6002 samples (12004 alleles) with coverage at this position. Based on protein sequence alignment, this amino acid position is well conserved in available vertebrate species, though methionine is the reference amino acid in one species.In addition, this alteration is predicted to be benign by PolyPhen analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Illumina Clinical Services Laboratory,Illumina RCV000316713 SCV000421501 uncertain significance Myopathy, early-onset, with fatal cardiomyopathy 2018-01-12 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 Clinical Services Laboratory,Illumina RCV000371276 SCV000421502 uncertain significance Limb-girdle muscular dystrophy, type 2J 2018-01-12 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 Clinical Services Laboratory,Illumina RCV000330851 SCV000421504 benign Tibial muscular dystrophy 2018-01-12 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 Clinical Services Laboratory,Illumina RCV000385420 SCV000421505 uncertain significance Dilated cardiomyopathy 1G 2018-01-12 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 Clinical Services Laboratory,Illumina RCV000291098 SCV000421506 benign Myopathy, myofibrillar, 9, with early respiratory failure 2018-01-12 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.
Invitae RCV001078567 SCV000765016 benign Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2020-09-01 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV001170788 SCV001333395 benign Cardiomyopathy 2018-02-20 criteria provided, single submitter clinical testing
Genetics and Genomics Program,Sidra Medicine RCV001293186 SCV001434184 likely benign Primary dilated cardiomyopathy criteria provided, single submitter research
Athena Diagnostics Inc RCV000155780 SCV001477173 benign not specified 2020-02-25 criteria provided, single submitter clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000172245 SCV001799344 likely benign not provided no assertion criteria provided clinical testing

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