ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.1261T>G (p.Ser421Ala)

dbSNP: rs878853864
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000228032 SCV000284375 uncertain significance Neurofibromatosis, type 1 2024-09-02 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 421 of the NF1 protein (p.Ser421Ala). This variant is not present in population databases (gnomAD no frequency). 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: 237513). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 RCV002317748 SCV001170831 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2024-09-11 criteria provided, single submitter clinical testing The p.S421A variant (also known as c.1261T>G) is located in coding exon 12 of the NF1 gene. The serine at codon 421 is replaced by alanine, an amino acid with similar properties. This change occurs in the first base pair of coding exon 12. This amino acid position is highly 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 this alteration remains unclear.
Genome-Nilou Lab RCV000228032 SCV002561887 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV004998510 SCV005623775 uncertain significance not provided 2023-11-24 criteria provided, single submitter clinical testing

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