Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center of Genomic medicine, |
RCV000223947 | SCV000598139 | pathogenic | Congenital myopathy 23 | 2016-09-23 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000128675 | SCV000709984 | pathogenic | not provided | 2023-04-05 | criteria provided, single submitter | clinical testing | Published functional studies support that c.20_22delAGA results in a protein with impaired localization, altered sarcomere structure, and impaired function (Mokbel et al., 2013; Davidson et al., 2013); In-frame deletion of 1 amino acids in a non-repeat region; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26307083, 31060721, 23378224, 23413262, 22980765, 27726070, 25214167, 33060286, 35579956, 36233295) |
Invitae | RCV000795370 | SCV000934833 | pathogenic | Arthrogryposis, distal, type 1A | 2022-11-05 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this variant affects TPM2 function (PMID: 23378224, 23413262, 26307083). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 140486). This variant is also known as c.19_21delAAG. This variant has been observed in individual(s) with autosomal dominant congenital myopathy (PMID: 22980765, 23378224, 23413262). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This variant, c.20_22del, results in the deletion of 1 amino acid(s) of the TPM2 protein (p.Lys7del), but otherwise preserves the integrity of the reading frame. |
3billion | RCV000223947 | SCV004013507 | pathogenic | Congenital myopathy 23 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Inframe deletion located in a nonrepeat region: predicted to change the length of the protein and disrupt normal protein function. Functional studies provide strong evidence of the variant having a damaging effect on the gene or gene product (PMID: 23378224, 23413262, 26307083). The variant has been observed in multiple (>3) similarly affected unrelated individuals (PMID: 22980765, 23378224, 23413262). The variant has been reported at least twice as pathogenic without evidence for the classification (ClinVar ID: VCV000140486). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. | |
TPM2 homepage - |
RCV000128675 | SCV000172315 | not provided | not provided | no assertion provided | not provided | ||
OMIM | RCV000223947 | SCV000280571 | pathogenic | Congenital myopathy 23 | 2023-06-01 | no assertion criteria provided | literature only |