Submissions for variant NM_005633.4(SOS1):c.1203-20T>C

gnomAD frequency: 0.01058  dbSNP: rs112906251

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000128196	SCV000171788	benign	not specified	2012-03-04	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
PreventionGenetics, part of Exact Sciences	RCV000128196	SCV000311182	benign	not specified		criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000157012	SCV001159523	benign	Noonan syndrome	2018-08-16	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000128196	SCV001361142	benign	not specified	2019-08-12	criteria provided, single submitter	clinical testing	Variant summary: SOS1 c.1203-20T>C alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0094 in 246642 control chromosomes, predominantly at a frequency of 0.014 within the Latino subpopulation in the gnomAD database, including 6 homozygotes. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 467-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in SOS1 causing Noonan Syndrome and Related Conditions phenotype (3e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. 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 benign.
Invitae	RCV002055815	SCV002394592	benign	RASopathy	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002467585	SCV002763455	benign	Noonan syndrome 4		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002467584	SCV002763456	benign	Fibromatosis, gingival, 1		criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528622	SCV001740632	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000128196	SCV001807812	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000128196	SCV001917727	benign	not specified		no assertion criteria provided	clinical testing