Submissions for variant NM_023110.3(FGFR1):c.2394_2395del (p.His798fs)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003051969	SCV003342944	uncertain significance	Hypogonadotropic hypogonadism 2 with or without anosmia; Pfeiffer syndrome	2024-01-24	criteria provided, single submitter	clinical testing	This sequence change results in a frameshift in the FGFR1 gene (p.His798Glnfs*187). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 25 amino acid(s) of the FGFR1 protein and extend the protein by 161 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FGFR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2127050). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant results in an extension of the FGFR1 protein. Other variant(s) that result in a similarly extended protein product (p.Arg852Thrfs*165) have been observed in individuals with FGFR1-related disease (PMID: 31605817). This suggests that these extensions may be clinically significant. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.