ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.3427C>T (p.His1143Tyr) (rs1555614963)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000540881 SCV000628519 likely pathogenic Neurofibromatosis, type 1 2019-02-06 criteria provided, single submitter clinical testing This sequence change replaces histidine with tyrosine at codon 1143 of the NF1 protein (p.His1143Tyr). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals with a clinical diagnosis or suspicion of neurofibromatosis type 1 (PMID: 12807981, 18546366) and it has been observed to be de novo in at least one affected individual (Invitae). ClinVar contains an entry for this variant (Variation ID: 457648). 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: "Probably Damaging"; Align-GVGD: "Class C0"). Analysis of the mRNA extracted from an individual with this variant revealed the presence of an alternatively spliced isoform, possibly through the use of a cryptic splice site (PMID: 12807981, 18546366). Whether this variant causes the observed splice disruption has not been experimentally studied. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000540881 SCV000781983 likely pathogenic Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing

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