Submissions for variant NM_023110.3(FGFR1):c.241A>G (p.Ile81Val)

gnomAD frequency: 0.00013  dbSNP: rs201574031

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001906268	SCV002172840	likely benign	Hypogonadotropic hypogonadism 2 with or without anosmia; Pfeiffer syndrome	2023-07-24	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV002267642	SCV002549858	uncertain significance	Pfeiffer syndrome	2022-07-11	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002509716	SCV002819724	uncertain significance	not specified	2022-12-21	criteria provided, single submitter	clinical testing	Variant summary: FGFR1 c.241A>G (p.Ile81Val) results in a conservative amino acid change located in the Immunoglobulin subtype 2 domain (IPR003598) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00014 in 280062 control chromosomes (gnomAD). To our knowledge, no occurrence of c.241A>G in individuals affected with FGFR1-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters have assessed the variant since 2014 without submitting evidence for independent evaluation: the variant was classified as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
PreventionGenetics, part of Exact Sciences	RCV004741134	SCV005348356	likely benign	FGFR1-related disorder	2024-03-29	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).