ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.2012C>G (p.Ala671Gly)

dbSNP: rs760900648
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002315838 SCV000674091 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2016-09-07 criteria provided, single submitter clinical testing The p.A671G variant (also known as c.2012C>G), located in coding exon 18 of the NF1 gene, results from a C to G substitution at nucleotide position 2012. The alanine at codon 671 is replaced by glycine, an amino acid with 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 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 175000 alleles 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 this alteration remains unclear.
Sema4, Sema4 RCV000566011 SCV002527440 uncertain significance Hereditary cancer-predisposing syndrome 2021-10-14 criteria provided, single submitter curation
Labcorp Genetics (formerly Invitae), Labcorp RCV002526913 SCV003204179 uncertain significance Neurofibromatosis, type 1 2024-07-01 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 671 of the NF1 protein (p.Ala671Gly). This variant is present in population databases (rs760900648, 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: 485952). 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 with a negative 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.
Baylor Genetics RCV003459391 SCV004190729 uncertain significance Juvenile myelomonocytic leukemia 2023-05-16 criteria provided, single submitter clinical testing

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