ClinVar Miner

Submissions for variant NM_000141.4(FGFR2):c.870G>T (p.Trp290Cys) (rs121918499)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV000014217 SCV000854609 pathogenic Pfeiffer syndrome 2018-11-18 no assertion criteria provided clinical testing
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000014217 SCV000328379 pathogenic Pfeiffer syndrome 2016-09-17 criteria provided, single submitter clinical testing
Invitae RCV000655418 SCV000777348 pathogenic FGFR2 related craniosynostosis 2017-11-14 criteria provided, single submitter clinical testing This sequence change replaces tryptophan with cysteine at codon 290 of the FGFR2 protein (p.Trp290Cys). The tryptophan residue is highly conserved and there is a large physicochemical difference between tryptophan and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with Pfeiffer syndrome (PMID: 9475591, 24036790), including individuals where the variant was confirmed to be de novo (PMID: 18618990, 27683237). ClinVar contains an entry for this variant (Variation ID: 13293). A different missense substitution at this codon (p.Trp290Arg) has been determined to be pathogenic (PMID: 7655462, 23431754, 16418739, 24656465, 24127277, 20503384). This suggests that the tryptophan residue is critical for FGFR2 protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000014217 SCV000034465 pathogenic Pfeiffer syndrome 2002-11-15 no assertion criteria provided literature only
OMIM RCV000014218 SCV000034466 pathogenic Craniofacial-skeletal-dermatologic dysplasia 2002-11-15 no assertion criteria provided literature only

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