ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.1307C>T (p.Ser436Leu)

dbSNP: rs755190083
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000806540 SCV000946544 uncertain significance Neurofibromatosis, type 1 2024-04-25 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 436 of the NF1 protein (p.Ser436Leu). This variant is present in population databases (rs755190083, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with NF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 651225). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NF1 protein function with a positive predictive value of 95%. 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.
Ambry Genetics RCV002318893 SCV001171161 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2024-10-25 criteria provided, single submitter clinical testing The p.S436L variant (also known as c.1307C>T), located in coding exon 12 of the NF1 gene, results from a C to T substitution at nucleotide position 1307. The serine at codon 436 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV000806540 SCV002561889 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing

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