ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.1721G>T (p.Ser574Ile) (rs1555613206)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000497781 SCV000590571 likely pathogenic not provided 2017-06-26 criteria provided, single submitter clinical testing The S574I variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). S574I is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position within the GTPase activating domain that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in the same residue (S574G/R/N/R) and in a nearby residue (L578R/P) have been reported in the Human Gene Mutation Database in association with neurofibromatosis type 1 (Stenson et al., 2014), supporting the functional importance of this region of the protein. In summary, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.

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