Submissions for variant NM_014967.5(FAN1):c.1090A>C (p.Asn364His)

gnomAD frequency: 0.00013  dbSNP: rs187082481

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000413270	SCV000491884	uncertain significance	not specified	2016-11-16	criteria provided, single submitter	clinical testing	The N364H variant in the FAN1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The N364H variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The N364H variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is not conserved. In silico analysis predicts this variant likely does not alter the protein structure/function. We interpret N364H as a variant of uncertain significance.
Fulgent Genetics, Fulgent Genetics	RCV000763956	SCV000894903	uncertain significance	Karyomegalic interstitial nephritis	2018-10-31	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000880502	SCV001023599	benign	not provided	2023-04-09	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003970093	SCV004781879	likely benign	FAN1-related disorder	2022-03-21	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).