Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000554157 | SCV000641095 | uncertain significance | Dyskeratosis congenita, autosomal dominant 1 | 2023-01-19 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 465765). 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. This variant is located within the hypervariable region that is not conserved in the TERC RNA component (PMID: 10721988, 21844345). The functional significance of this region is not well understood. This variant has not been reported in the literature in individuals affected with TERC-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant occurs in the TERC gene, which encodes an RNA molecule that does not result in a protein product. |
Prevention |
RCV003392385 | SCV004111836 | uncertain significance | TERC-related condition | 2023-02-21 | criteria provided, single submitter | clinical testing | The TERC n.202T>C is a noncoding alteration. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as uncertain significance or likely risk allele in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/465765/). A similar variant, n.202T>G, was reported in the homozygous state in two affected siblings with pulmonary fibrosis, nail dystrophy, abnormal skin pigmentation, and leukoplakia; however, further segregation studies in additional affected family members were not available (Family 18, Collopy et al. 2015. PubMed ID: 26024875). Functional studies showed that the n.202T>G variant possesses ~92% of wild-type telomerase activity (Collopy et al. 2015. PubMed ID: 26024875). At this time, the clinical significance of the n.202T>C variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Garcia Pulmonary Genetics Research Laboratory, |
RCV002509425 | SCV002547442 | likely risk allele | Pulmonary fibrosis | 2022-06-09 | no assertion criteria provided | research | Leukocyte telomere length (by qPCR) less than 10th percentile age-adjusted |