Total submissions: 12
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000059217 | SCV005624662 | uncertain significance | not provided | 2024-11-27 | criteria provided, single submitter | clinical testing | |
| Molecular Genetics, |
RCV000234372 | SCV004812506 | uncertain significance | Neurofibromatosis, type 1 | 2023-07-07 | criteria provided, single submitter | clinical testing | This sequence change in NF1 is predicted to replace threonine with alanine at codon 2631, p.(Thr2631Ala). The threonine residue is highly conserved (92/95 vertebrates, UCSC), and is not located in an annotated domain. There is a small physicochemical difference between threonine and alanine. The highest population minor allele frequency in the population database gnomAD v2.1 is 0.002% (2/113,630 alleles) in the European (non-Finnish) population. This variant has been reported in at least one proband with sporadic neurofibromatosis type 1 and an individual with pheochromocytoma explained by a pathogenic variant in RET (PMID: 8544190, 24694336). The prevalence of the variant in individuals with breast cancer is not significantly increased compared with the prevalence in controls (PMID: 33471991). Computational evidence predicts a benign effect for the missense substitution (REVEL = 0.279). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.6.1, this variant is classified as a VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: BP4. |
| Baylor Genetics | RCV003460655 | SCV004198254 | uncertain significance | Juvenile myelomonocytic leukemia | 2023-10-17 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003162465 | SCV003897004 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2021-01-15 | criteria provided, single submitter | clinical testing | The c.7828A>G (p.T2610A) alteration is located in exon 53 (coding exon 53) of the NF1 gene. This alteration results from a A to G substitution at nucleotide position 7828, causing the threonine (T) at amino acid position 2610 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Revvity Omics, |
RCV000059217 | SCV003815867 | uncertain significance | not provided | 2022-08-26 | criteria provided, single submitter | clinical testing | |
| Medical Genetics, |
RCV000234372 | SCV002567768 | uncertain significance | Neurofibromatosis, type 1 | 2022-08-17 | criteria provided, single submitter | clinical testing | |
| Genome- |
RCV000234372 | SCV002561155 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000059217 | SCV001787318 | uncertain significance | not provided | 2022-08-03 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Identified in a patient with cutaneous features of neurofibromatosis type 1 (Upadhyaya et al., 1995); This variant is associated with the following publications: (PMID: 24694336, 34426522, 25486365, 8544190) |
| Fulgent Genetics, |
RCV000764118 | SCV000895086 | uncertain significance | Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis | 2021-11-19 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000234372 | SCV000284517 | benign | Neurofibromatosis, type 1 | 2025-01-31 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000222408 | SCV000273712 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-02-04 | criteria provided, single submitter | clinical testing | The p.T2631A variant (also known as c.7891A>G or p.T2610A or c.7828A>G), located in coding exon 54 of the NF1 gene, results from an A to G substitution at nucleotide position 7891. The threonine at codon 2631 is replaced by alanine, an amino acid with similar properties. This alteration has beendetected in an individual with a clinical diagnosis of neurofibromatosis type 1 (NF1) (Upadhyaya M,J. Med. Genet. 1995 Sep; 32(9):706-10).This variant was previously reported in the SNPDatabase as rs199474793. This variant was not reported in population-based cohorts in the following databases:NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project.To date, this alteration has been detected with an allele frequency of approximately 0.003% (greater than 30000alleles tested) in our clinical cohort.This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive.Since supporting evidence is limited at this time, the clinical significance of p.T2631Aremains unclear. |
| Uni |
RCV000059217 | SCV000090746 | not provided | not provided | no assertion provided | not provided |