Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002319316 | SCV001183554 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2019-01-07 | criteria provided, single submitter | clinical testing | The p.S137C variant (also known as c.410C>G), located in coding exon 4 of the NF1 gene, results from a C to G substitution at nucleotide position 410. The serine at codon 137 is replaced by cysteine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. This alteration was identified in an individual in a cohort of individuals with a clinical diagnosis or clinical suspicion of neurofibromatosis type 1 (Xu W et al. Int. J. Mol. Med., 2014 Jul;34:53-60). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV001054187 | SCV001218490 | uncertain significance | Neurofibromatosis, type 1 | 2021-04-09 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in an individual with clinical features of neurofibromatosis type 1 (PMID: 24789688). This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with cysteine at codon 137 of the NF1 protein (p.Ser137Cys). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and cysteine. |
Genome- |
RCV001054187 | SCV002561454 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing |