Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000690257 | SCV000817938 | uncertain significance | Arthrogryposis, distal, type 1A | 2021-07-28 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with threonine at codon 155 of the TPM2 protein (p.Ala155Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 569587). This variant has been observed in individual(s) with distal arthrogryposis (PMID: 33060286). This variant is not present in population databases (ExAC no frequency). |
DASA | RCV002051885 | SCV002318964 | likely pathogenic | TPM2-related cap myopathy | 2022-03-25 | criteria provided, single submitter | clinical testing | The c.463G>A;p.(Ala155Thr) missense change has been observed in affected individual(s) (PMID: 31966463)-PS4_moderate. This variant is not present in population databases (rs1563929039- gnomAD; ABraOM no frequency - http://abraom.ib.usp.br.) - PM2. Pathogenic missense variant in this residue have been reported (PMID: 22832343) - PM5. Multiple lines of computational evidence support a deleterious effect on the gene or gene product - PP3. In summary, the currently available evidence indicates that the variant is likely pathogenic |
Gene |
RCV002249410 | SCV002520180 | likely pathogenic | not provided | 2022-04-11 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); This variant is associated with the following publications: (PMID: 30544720, 29792862, 28939420, 31155291, 32087052, 22832343, McAdow2021[article-not certified by peer review], 33060286, 23413262, Neissi2022[CaseReport], 31966463, 35052370) |
Institute of Human Genetics, |
RCV000690257 | SCV004027710 | pathogenic | Arthrogryposis, distal, type 1A | 2023-07-25 | criteria provided, single submitter | clinical testing | Criteria applied: PS3,PS2,PS4_MOD,PM1,PM5,PM2_SUP |