Submissions for variant NM_005633.4(SOS1):c.3769A>G (p.Thr1257Ala)

gnomAD frequency: 0.00006  dbSNP: rs553805862

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000176407	SCV000228058	uncertain significance	not provided	2015-02-17	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000176407	SCV001249219	uncertain significance	not provided	2019-07-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001344972	SCV001539065	likely benign	RASopathy	2025-01-12	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000176407	SCV002541809	uncertain significance	not provided	2021-10-21	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002362896	SCV002625961	uncertain significance	Cardiovascular phenotype	2024-07-29	criteria provided, single submitter	clinical testing	The p.T1257A variant (also known as c.3769A>G), located in coding exon 23 of the SOS1 gene, results from an A to G substitution at nucleotide position 3769. The threonine at codon 1257 is replaced by alanine, an amino acid with similar properties. This variant has been reported in a cohort with Noonan syndrome or related features; however, clinical detail was limited (Lepri F et al. Hum. Mutat., 2011 Jul;32:760-72). This amino acid position is well conserved in available vertebrate species. 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.
GeneDx	RCV000176407	SCV002757690	uncertain significance	not provided	2022-11-11	criteria provided, single submitter	clinical testing	Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant does not alter protein structure/function; Previously reported as a variant of uncertain significance in an individual with known or suspected Noonan syndrome (Lepri et al., 2011).; This variant is associated with the following publications: (PMID: 23891399, 29493581, 21387466)
Genome-Nilou Lab	RCV002467646	SCV002763535	uncertain significance	Noonan syndrome 4		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002467645	SCV002763536	uncertain significance	Fibromatosis, gingival, 1		criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002500487	SCV002814080	uncertain significance	Fibromatosis, gingival, 1; Noonan syndrome 4	2021-07-13	criteria provided, single submitter	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000176407	SCV001956169	likely benign	not provided		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000176407	SCV001962900	likely benign	not provided		no assertion criteria provided	clinical testing