Submissions for variant NM_006912.6(RIT1):c.235C>G (p.Gln79Glu)

dbSNP: rs1673398956

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001880009	SCV002317807	likely pathogenic	Noonan syndrome 8	2023-07-13	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 981604). This missense change has been observed in individual(s) with clinical features of Noonan syndrome (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 79 of the RIT1 protein (p.Gln79Glu). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
GeneDx	RCV003313201	SCV004012482	likely pathogenic	not provided	2023-07-13	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27226556, 35904599)
Genome-Nilou Lab	RCV001880009	SCV004050484	likely pathogenic	Noonan syndrome 8	2023-04-11	criteria provided, single submitter	clinical testing
Service de Génétique Moléculaire, Hôpital Robert Debré	RCV001261142	SCV001438551	uncertain significance	Noonan syndrome		no assertion criteria provided	clinical testing