Table 1 INF2 variants in the 10 index patients with Charcot–Marie–Tooth disease and Focal Segmental Glomerulosclerosis.

Family	Exon	Amino Acid	Nucleotide Change		Inheritance	gnomAD	ClinVAR		dbSNP	CADD	Reported CaAR	References
Family	Exon	Change	cDNA position	Zygosity	Inheritance	MAF	Interpre-tation	Accession	dbSNP	Score	Max R %	References
Single FSGS phenotype MIM613237
1 AI	Exon 3	p.Gly157Arg	c.469G > C	Hetero	AD	0	NA	NA	NA	25.1	ND	NA
2 AJ	Exon 3	p.Thr161Asn	c.482C > A	Hetero	AD	0	NA	NA	NA-	23.6	ND	Tsukaguchi H, 2019
3 SH	Exon 3	p.Leu162Pro	c.485 T > C	Hetero	AD	0	LP	VCV001184454.2	NA	25.3	9	Caridi G, 2014
4 HO	Exon 4	p.Asn202Ser	c.605A > G	Hetero	AD	0	LP	VCV001697256.1	NA	23.4	49	Santin S, 2011
5 TO	Exon 4	p.Arg218Trp	c.652C > T	Hetero	AD	0	P	VCV000001052.5	rs267606878	25.4	0	Brown E, 2010
6 KI	Exon 4	p.Glu220Lys	c.658G > A	Hetero	de novo	0	P	VCV000523533.7	rs530391015	24.7	33	Brown E, 2010
Dual CMT/FSGS phenotype MIM614455
7 OK	Exon 2	p.Leu69Pro	c.206 T > C	Hetero	mosaicism	0	VUS	VCV000637710.1	rs1595163820	26.9	0	Toyota K, 2013
8 NI	Exon 2	p.Gly73Asp	c.218G > A	Hetero	de novo	0	NA	NA	NA	26.5	0(Gly73Ser)	Hara M, 1984, Barua M, 2013
9 OS	Exon 2	p.Gly73Val	c.218G > T	Hetero	ND	0	P	VCV000472842.6	rs918089359	26.3	0(Gly73Ser)	Nagano C, 2020
10 YA	Exon 2	p.Val108Asp	c.323 T > A	Hetero	de novo	0	VUS	VCV000637711.1	rs1595164081	24.6	5	Toyota K, 2013

INF2 variants are annotated according to the nucleotide numbering of RefSeq NM_022489.4, where the A of the ATG-translation initiation codon is designated as position 1. Population allele frequency was obtained from the public database gnomAD (genome Aggregation Database); MAF, minor allele frequency; None of these variants were found in databases of Japanese healthy controls: HGVD, human genetic variation database; ToMMo, Integrative Japanese Genome Variation Database (iJGVD) of the Tohoku University Tohoku Medical Megabank Organization. AD, autosomal dominant. Scoring of deleteriousness was determined by Combined Annotation Dependent Depletion (CADD). In ClinVar annotations, variants are classified according to recommendation by the American College of Medical Genetics and Genomics (ACMG): P, Pathogenic; LP, Likely Pathogenic; VUS, Variant of uncertain significance. Calcium-dependent cellular actin organization (CaAR) was as described in a previous study¹⁰. CaAR measured in HeLa INF2 knock-out cells is shown as the percentage of cells with Max(R) values > 14.9. The values range from 100% (in control and cells expressing benign variants) to 0% (in cells expressing pathogenic variants). CMT, Charcot–Marie–Tooth Disease, FSGS, Focal segmental glomerulosclerosis, ND, not determined, NA, not applicable.

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