ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.5648A>G (p.Asn1883Ser) (rs864622647)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000205781 SCV000261557 uncertain significance Neurofibromatosis, type 1 2019-03-25 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 1883 of the NF1 protein (p.Asn1883Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been reported as de novo in an infant who also carried a de novo SOX9 variant (PMID: 27959697), therefore it is uncertain if the c.5648A>G NF1 variant is causative of disease in this individual. ClinVar contains an entry for this variant (Variation ID: 220757). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 RCV000205781 SCV000328744 likely pathogenic Neurofibromatosis, type 1 2016-05-01 no assertion criteria provided clinical testing Our laboratory reported two molecular diagnoses in NF1 (NM_000267.3:c.5648A>G) and SOX9 (NM_000346.3:c.1427T>C) in an individual with Pierre Robin Sequence, dysmorphic features, atrial septal defect with patent ductus arteriosus, hypertrophic cardiomyopathy, multiple cafe au lait spots, deep creases to palms and soles, a history of prematurity and a perinatal course complicated by anhydramnios, preterm premature rupture of membranes, pre-eclampsia and respiratory failure.

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