ClinVar Miner

Submissions for variant NM_004333.6(BRAF):c.1914T>A (p.Asp638Glu) (rs180177042)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000622900 SCV000742861 likely pathogenic Inborn genetic diseases 2017-09-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: POSITIVE: Relevant Alteration(s) Detected
Center for Human Genetics, Inc RCV000015015 SCV000781088 pathogenic Cardiofaciocutaneous syndrome 1 2016-11-01 criteria provided, single submitter clinical testing
Equipe Genetique des Anomalies du Developpement,Université de Bourgogne RCV000015015 SCV000965743 pathogenic Cardiofaciocutaneous syndrome 1 2016-01-01 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763164 SCV000893751 likely pathogenic Cardiofaciocutaneous syndrome 1; Lung cancer; Noonan syndrome 1; LEOPARD syndrome 3; Noonan syndrome 7 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000033337 SCV000057242 pathogenic not provided 2018-02-14 criteria provided, single submitter clinical testing The D638E variant has previously been published in multiple individuals with disorders on the Noonan syndrome spectrum, and was reported de novo in at least one (Rauen et al., 2006; Sarkozy et al., 2009). Functional in vitro studies have demonstrated that D638E results in decreased kinase activity (Rodriguez-Viciana et al., 2008). This variant is not observed in large population cohorts (Lek et al., 2016). The D638E variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. An alternate nucleotide change has been reported to cause the same missense variant (c.1914T>G), which has been reported in association with disorders on the Noonan syndrome spectrum (Sarkozy et al., 2009). Furthermore, the majority of missense variants in this gene are considered pathogenic. Based on the currently available information, we consider D638E to be pathogenic.
Institute of Human Genetics,Klinikum rechts der Isar RCV000015015 SCV000680155 pathogenic Cardiofaciocutaneous syndrome 1 2017-09-08 criteria provided, single submitter clinical testing
OMIM RCV000015015 SCV000035271 pathogenic Cardiofaciocutaneous syndrome 1 2006-08-01 no assertion criteria provided literature only

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