ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.3947A>C (p.His1316Pro)

dbSNP: rs751023085
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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 RCV002319296 SCV001183116 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2019-05-02 criteria provided, single submitter clinical testing The p.H1316P variant (also known as c.3947A>C), located in coding exon 29 of the NF1 gene, results from an A to C substitution at nucleotide position 3947. The histidine at codon 1316 is replaced by proline, an amino acid with similar 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001862189 SCV002236547 uncertain significance Neurofibromatosis, type 1 2021-01-05 criteria provided, single submitter clinical testing This sequence change replaces histidine with proline at codon 1316 of the NF1 protein (p.His1316Pro). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 824411). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.
Genome-Nilou Lab RCV001862189 SCV002560347 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004553560 SCV004115804 uncertain significance NF1-related disorder 2022-11-29 criteria provided, single submitter clinical testing The NF1 c.3947A>C variant is predicted to result in the amino acid substitution p.His1316Pro. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Of note, a different substitution at the same codon (p.His1316Gln) has been reported as a variant of uncertain significance in a study of germline pathogenic variants of breast cancer genes (Supplementary Data 1 in Momozawa et al. 2018. PubMed ID: 30287823). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. A family study of affected and unaffected individuals may clarify the significance of this variant.

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