ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.7961G>A (p.Arg2654Lys) (rs147207100)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000040730 SCV000064421 likely benign not specified 2012-02-09 criteria provided, single submitter clinical testing Arg2654Lys in exon 34 of TTN: This variant is not expected to have clinical sign ificance due to a lack of conservation across species, including mammals. Of not e, several mammals (rat, mouse, dog, megabat, and opossum) have a Lys at this po sition despite high nearby amino acid conservation. In addition, computational a nalyses (SIFT, AlignGVGD) do not suggest a high likelihood of impact to the prot ein. Furthermore, the Arg2654Lys has been identified in 0.1% (5/3738) of African American chromosomes from a broad population (NHLBI Exome Sequencing Project; h ttp://evs.gs.washington.edu/EVS, dbSNP rs147207100).
GeneDx RCV001703910 SCV000238040 likely benign not provided 2020-11-25 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 28973083)
Invitae RCV000459253 SCV000555220 likely benign Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2020-12-02 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000040730 SCV000701209 likely benign not specified 2017-02-02 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001130237 SCV001289807 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001130238 SCV001289808 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). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Clinical Services Laboratory,Illumina RCV001130239 SCV001289809 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001130240 SCV001289810 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). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Clinical Services Laboratory,Illumina RCV001135273 SCV001295047 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Genetics and Genomics Program,Sidra Medicine RCV001293136 SCV001434126 uncertain significance Primary dilated cardiomyopathy criteria provided, single submitter research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000040730 SCV001437393 benign not specified 2020-09-08 criteria provided, single submitter clinical testing Variant summary: TTN c.7961G>A (p.Arg2654Lys) results in a conservative amino acid change located in the I-band of the encoded protein sequence. Four of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0002 in 251268 control chromosomes, predominantly at a frequency of 0.003 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 8 fold of the estimated maximal expected allele frequency for a pathogenic variant in TTN causing Dilated Cardiomyopathy phenotype (0.00039), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified this variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Génétique et pathophysiologie de maladies neurodéveloppementales et épileptogènes, Institut de génétique et de biologie moléculaire et cellulaire RCV000201420 SCV000240003 benign Abnormality of neuronal migration 2014-10-31 no assertion criteria provided clinical testing

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