ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.106604T>C (p.Val35535Ala)

gnomAD frequency: 0.00006  dbSNP: rs368179478
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000540970 SCV000642598 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2023-12-19 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 35535 of the TTN protein (p.Val35535Ala). This variant is present in population databases (rs368179478, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with TTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 466758). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Not Available"; Align-GVGD: "Not Available". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant is located in the M band of TTN (PMID: 25589632). Non-truncating variants in this region may be relevant for neuromuscular disorders, but have not been definitively shown to cause cardiomyopathy (PMID: 23975875). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Eurofins Ntd Llc (ga) RCV000592815 SCV000705779 uncertain significance not provided 2017-01-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV002420448 SCV002677423 likely benign Cardiovascular phenotype 2020-09-18 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 RCV000592815 SCV003819180 uncertain significance not provided 2021-02-18 criteria provided, single submitter clinical testing

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