ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.4G>T (p.Ala2Ser)

dbSNP: rs2143144232
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001997805 SCV002254206 uncertain significance Neurofibromatosis, type 1 2021-09-08 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 affected with NF1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces alanine with serine at codon 2 of the NF1 protein (p.Ala2Ser). The alanine residue is weakly conserved and there is a moderate physicochemical difference between alanine and serine.
Ambry Genetics RCV002344125 SCV002645448 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2022-02-22 criteria provided, single submitter clinical testing The p.A2S variant (also known as c.4G>T), located in coding exon 1 of the NF1 gene, results from a G to T substitution at nucleotide position 4. The alanine at codon 2 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. 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 this alteration remains unclear.

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