ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.60976G>A (p.Ala20326Thr)

gnomAD frequency: 0.00008  dbSNP: rs370995867
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000609383 SCV000730395 likely benign not provided 2019-12-11 criteria provided, single submitter clinical testing
Invitae RCV000868058 SCV001009346 likely benign Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2023-12-13 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002271537 SCV002555637 likely benign not specified 2022-06-03 criteria provided, single submitter clinical testing Variant summary: TTN c.53272G>A (p.Ala17758Thr) results in a non-conservative amino acid change located in the A-band region of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00012 in 246926 control chromosomes in the gnomAD database, including 1 homozygote. This frequency is not significantly higher than estimated for a pathogenic variant in TTN causing Cardiomyopathy (0.00012 vs 0.00063), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.53272G>A in individuals affected with Dilated Cardiomyopathy/Limb-Girdle Muscular Dystrophy, Type 2J/TTN-related disorders and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Ambry Genetics RCV002457958 SCV002614831 likely benign Cardiovascular phenotype 2019-07-11 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Revvity Omics, Revvity RCV000609383 SCV004237459 uncertain significance not provided 2023-04-25 criteria provided, single submitter clinical testing

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