ClinVar Miner

Submissions for variant NM_005633.3(SOS1):c.1316A>C (p.Gln439Pro) (rs1057517861)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000414005 SCV000490906 likely pathogenic not provided 2015-04-29 criteria provided, single submitter clinical testing The Q439P missense substitution has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Q439P is a non-conservative amino acid substitution with a neutral, polar Glutamine residue being replaced by a non-polar Proline residue. It is located in a highly conserved region of the protein outside the known functional domains. Several pathogenic variants associated with Noonan syndrome have been reported in surrounding codons (G434R, I437T, C441Y) according to the Human Gene Mutation Database (Stenson et al. 2009). In silico algorithms predict Q439P is damaging to protein structure/function. The vast majority of missense changes in SOS1 are pathogenic; however, a small number of missense polymorphisms have been identified in this gene. Therefore, based on the available information, we interpret Q439P as a variant that is likely disease-causing.

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