ClinVar Miner

Submissions for variant NM_022970.3(FGFR2):c.1087+1340C>G (rs121918490)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000014176 SCV000328399 pathogenic Crouzon syndrome 2016-09-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV000623131 SCV000742731 pathogenic Inborn genetic diseases 2017-08-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: POSITIVE: Relevant Alteration(s) Detected
Invitae RCV000655419 SCV000777349 pathogenic FGFR2 related craniosynostosis 2018-02-19 criteria provided, single submitter clinical testing This sequence change replaces serine with cysteine at codon 354 of the FGFR2 protein (p.Ser354Cys). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in an individual affected with Crouzon syndrome (PMID: 7989400). In addition, this variant has been reported as a frequent cause of craniosynostosis and has been observed in several individuals affected with Crouzon syndrome (PMID: 25271085, 17693524, 24127277, 8528214, 11781872, 27028366, 7655462, 11173845). ClinVar contains an entry for this variant (Variation ID: 13265). The variant is also known as c.1073C>G (p.Ser354Cys) in the literature. Experimental studies have shown that this missense change results in an increase in constitutive protein activity in cell culture (PMID: 8755573). Other missense substitutions at this codon (p.Ser354Phe and p.Ser354Tyr) have also been reported in individuals affected with Crouzon syndrome (PMID:16418739, 12884424, 11173845). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000014176 SCV000034424 pathogenic Crouzon syndrome 1994-09-01 no assertion criteria provided literature only

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