Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001855974 | SCV002305735 | uncertain significance | not provided | 2021-09-17 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with alanine at codon 595 of the TTC37 protein (p.Pro595Ala). The proline residue is moderately conserved and there is a small physicochemical difference between proline and alanine. This variant is present in population databases (rs751343448, ExAC 0.2%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals with TTC37-related conditions. ClinVar contains an entry for this variant (Variation ID: 626200). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |
Center for Genomics, |
RCV001855974 | SCV003924180 | uncertain significance | not provided | 2021-03-30 | criteria provided, single submitter | clinical testing | TTC37 NM_014639.3 exon 19 p.Pro595Ala (c.1783C>G): This variant has not been reported in the literature but is present in 0.1% (58/30774) of South Asian alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs751343448). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |
Prevention |
RCV003947970 | SCV004758857 | likely benign | SKIC3-related disorder | 2022-11-14 | no assertion criteria provided | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |