ClinVar Miner

Submissions for variant NM_003289.4(TPM2):c.268C>T (p.Arg90Cys)

dbSNP: rs2490685001
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
3billion RCV006646554 SCV007539959 uncertain significance Arthrogryposis, distal, type 1A 2025-10-04 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v4.1.0 dataset (total allele frequency: <0.001%). Predicted Consequence/Location: Missense variant In silico tool predictions suggest damaging effect of the variant on gene or gene product [REVEL: 0.88 (>=0.6, sensitivity 0.68 and specificity 0.92); 3Cnet: 0.97 (> 0.75, sensitivity 0.96 and precision 0.92)]. A different missense change at the same codon (p.Arg90His) has been reported to be associated with TPM2-related disorder (ClinVar ID: VCV000617588). However the evidence of pathogenicity is insufficient at this time. Therefore, this variant is classified as Uncertain significance (PM2_M, PM5_P, PP3_P) according to the recommendation of ACMG/AMP guideline.
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV002280288 SCV002568308 uncertain significance not provided 2022-04-27 criteria provided, single submitter clinical testing PM2, PP3

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