Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001889523 | SCV002164898 | uncertain significance | not provided | 2022-07-18 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 1334 of the TTC37 protein (p.Thr1334Ala). This variant is present in population databases (rs186169356, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with TTC37-related conditions. ClinVar contains an entry for this variant (Variation ID: 1390335). 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 tolerated. 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, |
RCV002074433 | SCV002496016 | uncertain significance | Trichohepatoenteric syndrome 1 | 2021-03-15 | criteria provided, single submitter | clinical testing | TTC37 NM_014639.3 exon 38 p.Thr1334Ala (c.4000A>G): This variant has not been reported in the literature but is present in 0.02% (3/15284) of Latino alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/5-95484777-T-C?dataset=gnomad_r3). Evolutionary conservation suggests that this variant may impact the protein; computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |