ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.2572T>C (p.Ser858Pro)

dbSNP: rs587778550
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000213205 SCV000278759 uncertain significance Hereditary cancer-predisposing syndrome 2015-10-06 criteria provided, single submitter clinical testing The p.S858P variant (also known as c.2572T>C), located in coding exon 21 of the NF1 gene, results from a T to C substitution at nucleotide position 2572. The serine at codon 858 is replaced by proline, an amino acid with somewhat similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6501 samples (13002 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 55000alleles tested) in our clinical cohort.This amino acid position is not 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.S858Premains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001854661 SCV002164391 uncertain significance Neurofibromatosis, type 1 2021-05-07 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. 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 not expected to disrupt NF1 protein function. This variant has not been reported in the literature in individuals with NF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 134884). This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with proline at codon 858 of the NF1 protein (p.Ser858Pro). The serine residue is weakly conserved and there is a moderate physicochemical difference between serine and proline.
Genome-Nilou Lab RCV001854661 SCV002562059 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV004558313 SCV005047633 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2022-06-15 criteria provided, single submitter clinical testing The c.2572T>C (p.S858P) alteration is located in exon 21 (coding exon 21) of the NF1 gene. This alteration results from a T to C substitution at nucleotide position 2572, causing the serine (S) at amino acid position 858 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
ITMI RCV000121632 SCV000085830 not provided not specified 2013-09-19 no assertion provided reference population

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