ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.100432T>G (p.Trp33478Gly) (rs372304158)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000185071 SCV000237883 uncertain significance not specified 2017-05-26 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the TTN gene. While the W31837G variant has not been published in association with cardiomyopathy or skeletal muscle myopathy, it has been reported in a patient with a congenital heart defect (Grunert et al., 2014). This variant was reported as W33478G, c.100432 T>G due to the use of an alternate transcript in patient who harbored additional variants (Grunert et al., 2014). This variant is observed in 26/65986 (0.04%) alleles from individuals of European ancestry in the Exome Aggregation Consortium (ExAC) dataset (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The W31837G variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, this variant lacks observation in a significant number of affected individuals, segregation data, and functional evidence, which would further clarify its pathogenicity.
Illumina Clinical Services Laboratory,Illumina RCV000390641 SCV000420289 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 RCV000299494 SCV000420290 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 RCV000356693 SCV000420291 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 RCV000331220 SCV000420293 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 RCV000369666 SCV000420294 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 RCV000524719 SCV000642491 uncertain significance Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2017-11-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV000621440 SCV000736498 uncertain significance Cardiovascular phenotype 2018-09-19 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Athena Diagnostics Inc RCV000713946 SCV000844595 uncertain significance not provided 2017-09-08 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000713946 SCV000855092 uncertain significance not provided 2018-07-30 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000764298 SCV000895317 uncertain significance Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J; Tibial muscular dystrophy; Myopathy, myofibrillar, 9, with early respiratory failure; Myopathy, early-onset, with fatal cardiomyopathy; Familial hypertrophic cardiomyopathy 9 2018-10-31 criteria provided, single submitter clinical testing

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