Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000798528 | SCV000938148 | pathogenic | not provided | 2025-02-03 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr130*) in the NTHL1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NTHL1 are known to be pathogenic (PMID: 25938944, 26559593). This variant is present in population databases (rs371328106, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with NTHL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 644578). RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (internal data). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV001021416 | SCV001183030 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-02-01 | criteria provided, single submitter | clinical testing | The p.Y130* pathogenic mutation (also known as c.390C>A), located in coding exon 3 of the NTHL1 gene, results from a C to A substitution at nucleotide position 390. This changes the amino acid from a tyrosine to a stop codon within coding exon 3. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Gene |
RCV000798528 | SCV001794913 | pathogenic | not provided | 2023-08-15 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Published functional studies demonstrate a damaging affect: defective DNA repair activity and mutation suppression (Shinmura et al., 2019); This variant is associated with the following publications: (PMID: 31243857, 25938944, 26559593, 33980861, 30753826, 36196035, 30552997) |
| Myriad Genetics, |
RCV003458206 | SCV004188356 | pathogenic | Familial adenomatous polyposis 3 | 2023-09-05 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |
| Baylor Genetics | RCV003458206 | SCV004192135 | pathogenic | Familial adenomatous polyposis 3 | 2024-03-24 | criteria provided, single submitter | clinical testing |