Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000799280 | SCV000938935 | pathogenic | not provided | 2024-10-13 | 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with colorectal polyps and various cancers (PMID: 30753826). ClinVar contains an entry for this variant (Variation ID: 645235). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002352346 | SCV002620993 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-09-14 | criteria provided, single submitter | clinical testing | The p.Y130* variant (also known as c.390C>G), located in coding exon 3 of the NTHL1 gene, results from a C to G substitution at nucleotide position 390. This changes the amino acid from a tyrosine to a stop codon within coding exon 3. This variant has been identified likely in trans with a NTHL1 pathogenic variant in an individual diagnosed with clinical features consistent with NTHL1-associated polyposis (Grolleman JE et al. Cancer Cell, 2019 02;35:256-266.e5). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, 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. |
| Myriad Genetics, |
RCV003458208 | SCV004188360 | 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 | RCV003458208 | SCV004192201 | pathogenic | Familial adenomatous polyposis 3 | 2021-04-06 | criteria provided, single submitter | clinical testing |