Table 2.

Genetic findings and interpretation of SLC12A6 heterozygous variants.

Nucleotide change	c.620G>A		c.865G>A		c.1731_1733del		c.2036A>C
Amino acid change	p.Arg207His		p.Glu289Lys		p.Phe578del		p.Tyr679Ser
Zygosity	Heterozygous		Heterozygous		Heterozygous		Heterozygous
Alelle frequency‐gnomAD	0		0		0		0
Alelle frequency‐jMorp	0		0		0		0
Our control	–		–		–		–
SIFT/prediction	0	Damaging	0	Damaging	–	–	0	Damaging
PROVEAN/prediction	−4.57	Deleterious	−3.9	Deleterious	−12.78	Deleterious	−8.72	Deleterious
Polyphen2/prediction	0.998	Damaging	1	Damaging	–	–	0.995	Damaging
MutationAssesor/prediction	4.025	Damaging	4.27	Damaging	–	–	3.265	Damaging
FATHMM/prediction	−5.25	Damaging	−5.12	Damaging	–	–	−5.1	Damaging
Condel/prediction	0.73	Damaging	0.746	Damaging	–	–	0.673	Damaging
Dynamut
ΔΔG/prediction	−1.285 kcal/mol	Destabilizing	0.841 kcal/mol	Stabilizing	–	–	−2.425 kcal/mol	Destabilizing
ΔΔG (ENCOM)/prediction	−0.127 kcal/mol	Destabilizing	−0.108 kcal/mol	Destabilizing	–	–	−0.747 kcal/mol	Destabilizing
iMutant
RI/stability	8	Decrease	0	Decrease	–	–	8	Decrease
ACMG
Population data	PS4_Supporting PM2		PS4_Supporting PM2		PS4_Moderate PM2		PS4_Supporting PM2
In sillico data	PP3		PP3				PP3
De novo/segregation data	PM6		PP1_Moderate		PP1
Other data	PS3				PM4		PM5
Criteria	Pathogenic		Likely pathogenic		Likely pathogenic		Likely pathogenic

In silico analysis cut off: SIFT <0.05; PP2 >0.9; PROVEAN < −2.5; MA >1.9; FATHMM < −1.5; Condel >0.47.