Total submissions: 9
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000129314 | SCV000184076 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-01-03 | criteria provided, single submitter | clinical testing | The p.A2336T variant (also known as c.7006G>A), located in coding exon 47 of the NF1 gene, results from a G to A substitution at nucleotide position 7006. The alanine at codon 2336 is replaced by threonine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.009% (greater than 110000 alleles tested) in our clinical cohort. Based on protein sequence alignment, this amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be possibly damaging yet tolerated by PolyPhen and SIFT in silico analyses, respectively. Since supporting evidence is limited at this time, the clinical significance of p.A2336T remains unclear. |
| Labcorp Genetics |
RCV000226712 | SCV000284503 | likely benign | Neurofibromatosis, type 1 | 2024-12-09 | criteria provided, single submitter | clinical testing | |
| Mendelics | RCV000226712 | SCV000839159 | uncertain significance | Neurofibromatosis, type 1 | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001572206 | SCV001796806 | uncertain significance | not provided | 2023-04-07 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with breast cancer (Momozawa et al., 2018; Guindalini et al., 2022); This variant is associated with the following publications: (PMID: 25486365, 30287823, 35264596, 32980694) |
| Institute for Clinical Genetics, |
RCV001572206 | SCV002011201 | uncertain significance | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
| Sema4, |
RCV000129314 | SCV002530171 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-18 | criteria provided, single submitter | curation | |
| Genome- |
RCV000226712 | SCV002561023 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002362773 | SCV002664352 | likely benign | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2018-10-11 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Prevention |
RCV004737217 | SCV005356287 | uncertain significance | NF1-related disorder | 2024-08-04 | no assertion criteria provided | clinical testing | The NF1 c.7006G>A variant is predicted to result in the amino acid substitution p.Ala2336Thr. This variant was reported to segregate (data not shown) with neurofibromatosis in one family (Han et al 2001. PubMed ID: 11735023). This variant is reported in 0.012% of alleles in individuals of African descent in gnomAD and is interpreted as uncertain in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/141001/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |