Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000817862 | SCV000958445 | pathogenic | not provided | 2024-11-27 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Val127Glyfs*43) 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). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 660624). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002363139 | SCV002625259 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-12-05 | criteria provided, single submitter | clinical testing | The c.374dupC pathogenic mutation, located in coding exon 2 of the NTHL1 gene, results from a duplication of C at nucleotide position 374, causing a translational frameshift with a predicted alternate stop codon (p.V127Gfs*43). 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 |
RCV000817862 | SCV002762265 | likely pathogenic | not provided | 2022-12-07 | criteria provided, single submitter | clinical testing | Frameshift 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); Has not been previously published as pathogenic or benign to our knowledge |
| Myriad Genetics, |
RCV003458216 | SCV004188352 | pathogenic | Familial adenomatous polyposis 3 | 2023-09-05 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
| Baylor Genetics | RCV003458216 | SCV004192181 | likely pathogenic | Familial adenomatous polyposis 3 | 2024-01-22 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000817862 | SCV004222201 | likely pathogenic | not provided | 2023-02-23 | criteria provided, single submitter | clinical testing | This frameshift variant alters the translational reading frame of the NTHL1 mRNA and is predicted to cause the premature termination of NTHL1 protein synthesis. The variant has not been reported in individuals with NTHL1-related diseases in the published literature. Based on the available information, this variant is classified as likely pathogenic. |