Submissions for variant NM_006912.6(RIT1):c.375C>T (p.Asp125=)

gnomAD frequency: 0.00759  dbSNP: rs34831194

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000178921	SCV000231101	benign	not specified	2015-05-18	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000178921	SCV000269748	benign	not specified	2014-11-24	criteria provided, single submitter	clinical testing	Asp142Asp in exon 5 of RIT1: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. It has been identified in 2.6% (115/4406) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs34831194).
PreventionGenetics, part of Exact Sciences	RCV000178921	SCV000307148	benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV000588435	SCV000518593	benign	not provided	2016-04-20	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001082335	SCV000554657	benign	Noonan syndrome 8	2024-01-29	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588435	SCV000698733	benign	not provided	2017-07-04	criteria provided, single submitter	clinical testing	Variant summary: The RIT1 c.375C>T (p.Asp125Asp) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE site of SF2/ASF. However, these predictions have yet to be confirmed by functional studies. This variant was found in 291/121318 control chromosomes (5 homozygotes), predominantly observed in the African subpopulation at a frequency of 0.02665 (277/10394). This frequency is about 2132 times the estimated maximal expected allele frequency of a pathogenic RIT1 variant (0.0000125), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories/reputable databases have classified this variant as benign. Taken together, this variant is classified as benign.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001813423	SCV002060615	benign	Noonan syndrome and Noonan-related syndrome	2021-06-07	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000178921	SCV002066083	benign	not specified	2018-06-05	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002345624	SCV002623023	benign	Cardiovascular phenotype	2019-01-07	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.
Genome-Nilou Lab	RCV001082335	SCV004050451	benign	Noonan syndrome 8	2023-04-11	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001082335	SCV004564932	benign	Noonan syndrome 8	2023-10-13	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000588435	SCV005282247	benign	not provided		criteria provided, single submitter	not provided