ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.95312G>A (p.Arg31771Lys)

gnomAD frequency: 0.00002  dbSNP: rs397517760
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000040825 SCV000064516 uncertain significance not specified 2012-01-09 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Arg29203Lys var iant (TTN) has not been reported in the literature nor previously identified by our laboratory. Arginine (Arg) at position 29203 is not conserved in mammals or lower species, with several species carrying a lysine (Lys; this variant), incre asing the likelihood that a change would be tolerated. Computational tools (Alig nGVGD, SIFT) predict that a change to lysine would not impact the protein, thoug h the accuracy of these tools is unknown. Although this data suggests that the A rg29203Lys variant may be benign, additional information is needed to fully asse ss its clinical significance.
Invitae RCV002513570 SCV003306857 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2023-01-10 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 31771 of the TTN protein (p.Arg31771Lys). 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. This variant is located in the A band of TTN (PMID: 25589632). Variants in this region may be relevant for cardiac or neuromuscular disorders (PMID: 25589632, 23975875). 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 lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 47556). This variant has not been reported in the literature in individuals affected with TTN-related conditions. This variant is present in population databases (rs397517760, gnomAD 0.01%).

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