Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002319317 | SCV001183564 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2018-03-09 | criteria provided, single submitter | clinical testing | The p.V1371M variant (also known as c.4111G>A) is located in coding exon 31 of the NF1 gene. The valine at codon 1371 is replaced by methionine, an amino acid with highly similar properties. This change occurs in the first base pair of coding exon 31. This amino acid position is highly 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 this alteration remains unclear. |
Genetic Services Laboratory, |
RCV001819733 | SCV002064825 | uncertain significance | not specified | 2020-10-14 | criteria provided, single submitter | clinical testing | DNA sequence analysis of the NF1 gene demonstrated a sequence change, c.4111G>A, in exon 31 that results in an amino acid change, p.Val1371Met. This sequence change does not appear to have been previously described in patients with NF1-related disorders and has also not been described in population databases (gnomAD, ExAC). The p.Val1371Met change affects a highly conserved amino acid residue located in a domain of the NF1 protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Val1371Met substitution. Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Val1371Met change remains unknown at this time. |