Submissions for variant NM_005633.4(SOS1):c.3257C>T (p.Pro1086Leu)

gnomAD frequency: 0.00001  dbSNP: rs730881028

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000159130	SCV000209074	uncertain significance	not provided	2012-05-10	criteria provided, single submitter	clinical testing	The P1086L missense substitution has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. P1086L is a non-conservative amnio acid substitution as a Proline residue with a unique ring structure is replaced with a Leucine residue at a position that is highly conserved across species and related proteins. The NHLBI ESP Exome Variant Server reports P1086L was not observed in approximately 5,000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. However, mutations beyond codon Proline 894 have not been reported in the literature. The variant is found in NOONAN panel(s).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001420900	SCV001623339	uncertain significance	not specified	2021-04-26	criteria provided, single submitter	clinical testing	Variant summary: SOS1 c.3257C>T (p.Pro1086Leu) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251050 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3257C>T in individuals affected with Noonan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Genome-Nilou Lab	RCV002467524	SCV002763235	uncertain significance	Noonan syndrome 4		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002467523	SCV002763236	uncertain significance	Fibromatosis, gingival, 1		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004018721	SCV005023786	uncertain significance	Cardiovascular phenotype	2023-10-27	criteria provided, single submitter	clinical testing	The p.P1086L variant (also known as c.3257C>T), located in coding exon 20 of the SOS1 gene, results from a C to T substitution at nucleotide position 3257. The proline at codon 1086 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.