ClinVar Miner

Submissions for variant NM_004333.6(BRAF):c.721A>C (p.Thr241Pro) (rs387906661)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000211752 SCV000061618 pathogenic Cardio-facio-cutaneous syndrome 2012-06-26 criteria provided, single submitter clinical testing The Thr241Pro variant in BRAF has been reported in the literature in four indivi duals with clinical features of Cardio-facio-cutaneous syndrome, LEOPARD, or Cos tello syndrome (Nava 2007, Schulz 2008, Sarkozy 2009). This variant was reported to have occurred de novo in three of those individuals. Therefore, this variant meets our criteria to be classified as pathogenic.
Molecular Diagnostics Lab,Nemours Alfred I. duPont Hospital for Children RCV000207516 SCV000263060 likely pathogenic not provided 2015-07-23 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000515363 SCV000611251 pathogenic Cardiofaciocutaneous syndrome 1; Lung cancer; Noonan syndrome 1; LEOPARD syndrome 3; Noonan syndrome 7 2017-05-18 criteria provided, single submitter clinical testing
Invitae RCV000654966 SCV000776876 pathogenic Rasopathy 2017-11-27 criteria provided, single submitter clinical testing This sequence change replaces threonine with proline at codon 241 of the BRAF protein (p.Thr241Pro). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in individuals affected with cardio–facio–cutaneous syndrome (PMID: 17704260, 18042262). ClinVar contains an entry for this variant (Variation ID: 29807). Experimental studies have shown that this missense change p.Thr241Pro reduced amplitudes of synaptic responses in rat neurons (PMID: 28404629). A different missense substitution at this codon (p.The241Met) has been determined to be pathogenic (PMID: 19206169). This suggests that the threonine residue is critical for BRAF protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV000207516 SCV000927223 pathogenic not provided 2017-04-07 criteria provided, single submitter clinical testing
OMIM RCV000022680 SCV000043969 pathogenic Cardiofaciocutaneous syndrome 1 2009-04-01 no assertion criteria provided literature only
OMIM RCV000022681 SCV000043970 pathogenic LEOPARD syndrome 3 2009-04-01 no assertion criteria provided literature only
GeneReviews RCV000055896 SCV000086904 pathologic Noonan syndrome with multiple lentigines 2010-11-16 no assertion criteria provided curation Converted during submission to Pathogenic.

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