Submissions for variant NM_022489.4(INF2):c.2053A>G (p.Ile685Val)

gnomAD frequency: 0.00016  dbSNP: rs199526439

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000301022	SCV000385281	likely benign	Focal segmental glomerulosclerosis 5	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Invitae	RCV000527454	SCV000652085	uncertain significance	Focal segmental glomerulosclerosis 5; Charcot-Marie-Tooth disease dominant intermediate E	2024-01-19	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 685 of the INF2 protein (p.Ile685Val). This variant is present in population databases (rs199526439, gnomAD 0.03%). This missense change has been observed in individual(s) with steroid-resistant nephrotic syndrome (PMID: 23349334, 23515051). ClinVar contains an entry for this variant (Variation ID: 312700). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Not Available"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
GeneDx	RCV001508744	SCV000721862	likely benign	not provided	2020-12-24	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 23349334, 32451589, 32444357)
Mayo Clinic Laboratories, Mayo Clinic	RCV001508744	SCV001715090	uncertain significance	not provided	2019-04-14	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002418164	SCV002725543	likely benign	Inborn genetic diseases	2022-02-03	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.