Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000220588 | SCV000274138 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-02-22 | criteria provided, single submitter | clinical testing | The p.C632S variant (also known as c.1894T>A), located in coding exon 17 of the NF1 gene, results from a T to A substitution at nucleotide position 1894. The cysteine at codon 632 is replaced by serine, an amino acid with dissimilar properties.This alteration was previously reported in 1/681 individuals in a healthy, ancestrally diverse cohort via genome sequencing, having been detected in 1/331European individuals in this cohort (BodianDL et al.PLoSONE2014;9(4):e94554). This variant was previously reported in the SNPDatabase as rs370789267. Based on data from the NHLBI Exome Sequencing Project (ESP), the A allele has an overall frequency of approximately 0.01% (1/13006) total alleles studied, having been observed in0.01% (1/8600) European American alleles. To date, this alteration has been detected with an allele frequency of approximately 0.004% (greater than 110000 alleles tested) in our clinical cohort. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of p.C632S remains unclear. |
Invitae | RCV000234708 | SCV000284394 | likely benign | Neurofibromatosis, type 1 | 2024-01-28 | criteria provided, single submitter | clinical testing | |
Athena Diagnostics | RCV000712402 | SCV000842884 | uncertain significance | not provided | 2018-03-07 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000121630 | SCV000917881 | uncertain significance | not specified | 2021-03-19 | criteria provided, single submitter | clinical testing | Variant summary: NF1 c.1894T>A (p.Cys632Ser) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251898 control chromosomes (gnomAD and publication data). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1894T>A in individuals affected with Neurofibromatosis Type 1 and no experimental evidence demonstrating its impact on protein function have been reported. One co-occurrence with another pathogenic variant has been reported internally (MSH6 c.3920_3923dupATCT, p.P1309fs*11), providing supporting evidence for a benign role. Four ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Baylor Genetics | RCV000234708 | SCV001482852 | uncertain significance | Neurofibromatosis, type 1 | 2019-03-22 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
Gene |
RCV000712402 | SCV001811698 | likely benign | not provided | 2023-04-25 | criteria provided, single submitter | clinical testing | See Variant Classification Assertion Criteria. |
Sema4, |
RCV000220588 | SCV002527426 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-10 | criteria provided, single submitter | curation | |
Genome- |
RCV000234708 | SCV002561958 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002483222 | SCV002789985 | uncertain significance | Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis | 2021-11-10 | criteria provided, single submitter | clinical testing | |
ITMI | RCV000121630 | SCV000085828 | not provided | not specified | 2013-09-19 | no assertion provided | reference population |