Submissions for variant NM_005633.4(SOS1):c.1964C>T (p.Pro655Leu)

gnomAD frequency: 0.00787  dbSNP: rs56219475

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen RASopathy Variant Curation Expert Panel	RCV000149843	SCV000616516	benign	RASopathy	2017-04-18	reviewed by expert panel	curation	The filtering allele frequency of the c.1964C>T (p.Pro655Leu) variant in the SOS1 gene is 1.153% (803/65674) of European chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BA1; PMID:29493581)
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038527	SCV000062205	benign	not specified	2006-10-28	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000038527	SCV000113237	benign	not specified	2013-06-07	criteria provided, single submitter	clinical testing
Invitae	RCV000149843	SCV000260896	benign	RASopathy	2024-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000038527	SCV000311187	benign	not specified		criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001572796	SCV000605234	benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852770	SCV000995489	benign	Arrhythmogenic right ventricular cardiomyopathy	2017-02-02	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001141306	SCV001301644	likely benign	Noonan syndrome 4	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
GeneDx	RCV001572796	SCV001943958	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 17143282, 20981092, 23487764, 17143285, 27153395, 32514133)
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001813292	SCV002060638	benign	Noonan syndrome and Noonan-related syndrome	2021-04-16	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001572796	SCV002544024	benign	not provided	2024-05-01	criteria provided, single submitter	clinical testing	SOS1: BS1, BS2
Ambry Genetics	RCV002415452	SCV002722235	benign	Cardiovascular phenotype	2017-08-24	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Baylor Genetics	RCV000149843	SCV000196688	benign	RASopathy		no assertion criteria provided	clinical testing	Variant classified using ACMG guidelines
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	RCV000038527	SCV000207679	benign	not specified	2015-01-15	no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001572796	SCV001797724	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000038527	SCV001808885	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000038527	SCV001922697	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000038527	SCV001959319	benign	not specified		no assertion criteria provided	clinical testing