ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.21656C>T (p.Ser7219Phe) (rs201029552)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000213535 SCV000238300 uncertain significance not specified 2015-11-23 criteria provided, single submitter clinical testing Missense variants in the TTN gene are considered 'unclassified' if they are not previously reported in the literature and do not have >1% frequency in the population to be considered a polymorphism. Research indicates that truncating mutations in the TTN gene are expected to account for approximately 25% of familial and 18% of sporadic idiopathic DCM; however, truncating variants in the TTN gene have been reported in approximately 3% of reported control alleles. There has been little investigation into non-truncating variants. (Herman D et al. Truncations of titin causing dilated cardiomyopathy. N Eng J Med 366:619-628, 2012) The variant is found in CARDIOMYOPATHY panel(s).
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000213535 SCV000272594 benign not specified 2019-05-22 criteria provided, single submitter clinical testing The p.Ser5975Phe variant in TTN is classified as likely benign due to a lack of conservation across species. Four mammals (pig, horse, white rhinoceros and elephant) carry a phenylalanine (Phe) at this position despite high nearby amino acid conservation. It has also been identified in 0.04% (14/35192) of Latino chromosomes by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BS1, BP4_Strong.
Ambry Genetics RCV000251604 SCV000318161 uncertain significance Inborn genetic diseases 2014-06-05 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: UNCERTAIN: Alteration(s) of Uncertain Clinical Significance Detected
Illumina Clinical Services Laboratory,Illumina RCV000296518 SCV000424340 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 RCV000335093 SCV000424341 likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000401816 SCV000424342 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 RCV000338709 SCV000424344 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 RCV000406874 SCV000424345 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.
Invitae RCV000470210 SCV000542321 uncertain significance Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2018-01-04 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000725490 SCV000700993 uncertain significance not provided 2016-11-17 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000770079 SCV000901505 uncertain significance Cardiomyopathy 2016-08-09 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000725490 SCV001153047 uncertain significance not provided 2017-04-01 criteria provided, single submitter clinical testing

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