ClinVar Miner

Submissions for variant NM_030662.4(MAP2K2):c.335G>T (p.Arg112Leu)

dbSNP: rs2041142587
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001038482 SCV001201952 likely pathogenic RASopathy 2019-12-17 criteria provided, single submitter clinical testing This variant has been observed in an individual with clinical features of Noonan syndrome (Invitae). In at least one individual the variant was observed to be de novo. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with leucine at codon 112 of the MAP2K2 protein (p.Arg112Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV003741245 SCV004564457 likely pathogenic Cardiofaciocutaneous syndrome 4 2023-03-14 criteria provided, single submitter clinical testing The MAP2K2 c.335G>T; p.Arg112Leu variant (rs2041142587) is reported in an individual with cardio-facio-cutaneous syndrome (Bertola 2020), and is also reported in ClinVar (Variation ID: 837201). One submission in ClinVar reports that this variant has been seen de novo in an individual with clinical features of Noonan syndrome (Accession: SCV001201952.4). This variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. Computational analyses predict that this variant is deleterious (REVEL: 0.925). Based on available information, this variant is considered to be likely pathogenic. References: Bertola DR et al. Phenotype-genotype analysis of 242 individuals with RASopathies: 18-year experience of a tertiary center in Brazil. Am J Med Genet C Semin Med Genet. 2020 Dec;184(4):896-911. PMID: 33128510.

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