Submissions for variant NM_023110.3(FGFR1):c.1368G>T (p.Met456Ile)

gnomAD frequency: 0.00047  dbSNP: rs200776757

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000343209	SCV000473618	benign	Trigonocephaly 1	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000284766	SCV000473620	benign	Osteoglophonic dysplasia	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000337400	SCV000473621	benign	Craniosynostosis syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000404673	SCV000473622	likely benign	Hypogonadotropic hypogonadism 2 with or without anosmia	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000408775	SCV000484838	likely benign	Craniosynostosis, nonspecific	2016-11-03	criteria provided, single submitter	clinical testing
Invitae	RCV000703651	SCV000832561	likely benign	Hypogonadotropic hypogonadism 2 with or without anosmia; Pfeiffer syndrome	2024-01-05	criteria provided, single submitter	clinical testing
GeneDx	RCV001528843	SCV001790852	likely benign	not provided	2021-03-17	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 29419413, 25077900)
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV001528843	SCV002010667	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Reproductive Endocrine Unit, Massachusetts General Hospital	RCV000404673	SCV003932558	uncertain significance	Hypogonadotropic hypogonadism 2 with or without anosmia	2023-05-04	criteria provided, single submitter	research	The variant has been classified as VUS based on the variant meeting the following ACMG Criteria: PP1,PP2,BP4,BP4.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528843	SCV001741270	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001528843	SCV001954766	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001528843	SCV001971733	likely benign	not provided		no assertion criteria provided	clinical testing