ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.49406T>A (p.Leu16469His)

gnomAD frequency: 0.00006  dbSNP: rs72677245
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001087387 SCV000555605 likely benign Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2024-01-16 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000727401 SCV000708239 uncertain significance not provided 2017-05-11 criteria provided, single submitter clinical testing
GeneDx RCV000727401 SCV000728545 likely benign not provided 2019-04-10 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 26567375)
Athena Diagnostics Inc RCV000596356 SCV001475002 benign not specified 2020-07-31 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000596356 SCV001983692 likely benign not specified 2021-09-21 criteria provided, single submitter clinical testing Variant summary: TTN c.41702T>A (p.Leu13901His) results in a non-conservative amino acid change located in the A-Band of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00034 in 246398 control chromosomes, predominantly at a frequency of 0.0025 within the Latino subpopulation in the gnomAD database. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 4 fold of the estimated maximal expected allele frequency for a pathogenic variant in TTN causing Cardiomyopathy phenotype (0.00063), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. The variant was reported in a patient with DCM, without strong evidence for causality (Begay_2015). To our knowledge, no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Three submitters classified as likely benign/benign while one classified as VUS. Based on the evidence outlined above, the variant was classified as likely benign.
Revvity Omics, Revvity Omics RCV000727401 SCV003825496 uncertain significance not provided 2023-08-29 criteria provided, single submitter clinical testing

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