Submissions for variant NM_005633.4(SOS1):c.3329C>G (p.Ser1110Trp)

dbSNP: rs572955351

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000159139	SCV000209083	uncertain significance	not provided	2013-05-21	criteria provided, single submitter	clinical testing	The S1110W missense substitution has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI ESP Exome Variant Server reports S1110W was not observed in approximately 6,500 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. S1110W is a non-conservative amino acid substitution as a polar Serine residue is replaced with a non-polar Tryptophan residue at a position that is well conserved across species. Additionally, in silico algorithms predict S1110W is a damaging change. However, the S1110W variant is not located within any known functional domain of the protein and mutations associated with Noonan syndrome have not been reported in the literature beyond codon Proline 894. Therefore, the S1110W missense change is likely a rare benign variant; however, the possibility that is a disease-causing mutation cannot be excluded. The variant is found in SOS1 panel(s).
Ambry Genetics	RCV002321669	SCV002609055	uncertain significance	Cardiovascular phenotype	2021-12-23	criteria provided, single submitter	clinical testing	The p.S1110W variant (also known as c.3329C>G), located in coding exon 20 of the SOS1 gene, results from a C to G substitution at nucleotide position 3329. The serine at codon 1110 is replaced by tryptophan, an amino acid with highly dissimilar 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.
Genome-Nilou Lab	RCV002467628	SCV002763228	uncertain significance	Noonan syndrome 4		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002467627	SCV002763229	uncertain significance	Fibromatosis, gingival, 1		criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002516397	SCV003023894	likely benign	RASopathy	2023-11-08	criteria provided, single submitter	clinical testing