ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.4963G>A (p.Ala1655Thr) (rs756450772)

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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 RCV000223466 SCV000276483 uncertain significance Hereditary cancer-predisposing syndrome 2015-06-15 criteria provided, single submitter clinical testing Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;Rarity in general population databases (dbsnp, esp, 1000 genomes);Insufficient or conflicting evidence;In silico models in agreement (benign)
Invitae RCV000463631 SCV000542197 uncertain significance Neurofibromatosis, type 1 2018-07-17 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 1655 of the NF1 protein (p.Ala1655Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs756450772, ExAC 0.009%). This variant has been reported in an individual affected with neurofibromatosis type 1 (PMID: 22105171). ClinVar contains an entry for this variant (Variation ID: 232362). Experimental studies have shown that this missense change did not affect the interaction between the leucine rich domain (LRD) and valosin-containing protein (VCP) that are important for dendritic spine density. However, the clinical significance of this finding is unknown (PMID: 22105171). 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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