ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.102271C>T (p.Arg34091Trp) (rs140319117)

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000154875 SCV000204557 likely benign not specified 2017-06-05 criteria provided, single submitter clinical testing p.Arg31523Trp in exon 307 of TTN: This variant is not expected to have clinical significance because it has been identified in 0.3% (33/10126) of Ashkenazi Jewi sh chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadin stitute.org/; dbSNP rs140319117).
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000713953 SCV000229375 uncertain significance not provided 2018-09-14 criteria provided, single submitter clinical testing
GeneDx RCV000154875 SCV000236911 uncertain significance not specified 2015-09-24 criteria provided, single submitter clinical testing p.Arg32450Trp (CGG>TGG): c.97348 C>T in exon 308 of the TTN gene (NM_001256850.1). The R32450W variant in the TTN gene has been published in two Swedish families with Hereditary Myopathy with Early Respiratory Failure (HMERF) (reported as R279W) (Lange S et al., 2005). HMERF is an autosomal dominant adult-onset myopathy with early respiratory muscle involvement, proximal weakness of the upper and lower extremities. To our knowledge, no cardiomyopathy has been reported in HMERF. Lange S et al., reported that R32450W occurs in the Kinase domain of the titin protein, at a residue that is conserved across evolution. However, the NHLBI Exome Sequencing Project reports R32450W was observed in 13/8,276 alleles from individuals of European background, and this variant is listed in 1000 genomes in 2/756 European alleles, indicating this change may be a benign variant in this population. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in DCM,CARDIOMYOPATHY,DCM-CRDM panel(s).
Invitae RCV001086721 SCV000555083 likely benign Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2020-12-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV000621822 SCV000735076 likely benign Cardiovascular phenotype 2019-11-21 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other data supporting benign classification
Athena Diagnostics Inc RCV000154875 SCV000844602 benign not specified 2020-06-29 criteria provided, single submitter clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000852776 SCV000995499 likely benign Primary dilated cardiomyopathy; Heart failure 2018-07-03 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001134221 SCV001293954 uncertain significance Myopathy, early-onset, with fatal cardiomyopathy 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV000119019 SCV001293955 benign Myopathy, myofibrillar, 9, with early respiratory failure 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Illumina Clinical Services Laboratory,Illumina RCV001134222 SCV001293956 uncertain significance Limb-girdle muscular dystrophy, type 2J 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV000509179 SCV001293957 benign Tibial muscular dystrophy 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Illumina Clinical Services Laboratory,Illumina RCV001134223 SCV001293958 uncertain significance Dilated cardiomyopathy 1G 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
GeneReviews RCV000119019 SCV000153721 uncertain significance Myopathy, myofibrillar, 9, with early respiratory failure 2014-02-27 no assertion criteria provided literature only
GenomeConnect, ClinGen RCV000509179 SCV000607067 not provided Tibial muscular dystrophy no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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