Submissions for variant NM_005633.4(SOS1):c.2253T>G (p.Asn751Lys)

dbSNP: rs1553354376

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000523565	SCV000616984	uncertain significance	not provided	2017-08-08	criteria provided, single submitter	clinical testing	The N751K 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). N751K is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals; however, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Ambry Genetics	RCV002448569	SCV002736496	uncertain significance	Cardiovascular phenotype	2021-11-09	criteria provided, single submitter	clinical testing	The p.N751K variant (also known as c.2253T>G), located in coding exon 14 of the SOS1 gene, results from a T to G substitution at nucleotide position 2253. The asparagine at codon 751 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab	RCV002467856	SCV002763314	uncertain significance	Noonan syndrome 4		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002467855	SCV002763315	uncertain significance	Fibromatosis, gingival, 1		criteria provided, single submitter	clinical testing