ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.3812T>C (p.Met1271Thr) (rs876659801)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000217912 SCV000276639 uncertain significance Hereditary cancer-predisposing syndrome 2015-06-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),Insufficient or conflicting evidence
Invitae RCV000468737 SCV000541977 uncertain significance Neurofibromatosis, type 1 2018-12-30 criteria provided, single submitter clinical testing This sequence change replaces methionine with threonine at codon 1271 of the NF1 protein (p.Met1271Thr). The methionine residue is moderately conserved and there is a moderate physicochemical difference between methionine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual with suspected neurofibromatosis type 1 (Invitae). However, in that individual pathogenic allele[s] were also identified in NF1, which suggests that this c.3812T>C variant was not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 232492). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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