TABLE 1.

Illustrative examples of human Hsp60 missense mutations in sequenced genomes.

Mutation	Disease	Source	Pathogenicity1	Pathogenicity prediction by PolyPhen-2
p.D29G	Hypomyelinating leukodystrophy	(Magen et al., 2008; Parnas et al., 2009; Bross and Fernandez-Guerra, 2016); ClinVar	Proven	Benign
p.A34V	N. R.2	gnomAD	Unlikely	Benign
p.D35G	N. R.	gnomAD	Unlikely	Benign
p.M55L	N. R.	gnomAD	Unlikely	Benign
p.V98I	Spastic paraplegia 13 (SPG13)	(Fontaine et al., 2000; Hansen et al., 2002; Bross et al., 2008; Bross and Fernandez-Guerra, 2016); ClinVar	Proven	Possibly damaging
p.E129K	Spastic paraplegia	ClinVar; gnomAD; NHLBI ESP	Likely	Possibly damaging
p.K133E	N. R.	ClinVar	Likely	Benign
p.R221Q	Hereditary spastic paraplegia 13	ClinVar; gnomAD; NHBLI ESP	Likely	Benign
p.Y223C	N. R.	gnomAD	Likely	Probably damaging
p.N265S	Hereditary spastic paraplegia 13	(Bross and Fernandez-Guerra, 2016); ClinVar; gnomAD; NHLBI ESP	Likely	Possibly damaging
p.V287I	Hereditary spastic paraplegia 13	ClinVar	Likely	Benign
p.E328V	N. R.	gnomAD	Unlikely	Possibly damaging
p.Q461E	Autosomal dominant spastic paraplegia (SPG13)	(Hansen et al., 2007; Bross and Fernandez-Guerra, 2016)	Proven	Probably damaging
p.K473Q	N. R.	gnomAD	Likely	Benign
p.S488T	N. R.	gnomAD	Likely	Possibly damaging
p.D504N	N. R.	gnomAD	Unlikely	Benign
p. A505T	N. R.	gnomAD	Unlikely	Benign
p.M506V	N. R.	gnomAD	Unlikely	Benign

¹Assessed by the study of the possible consequence of mutations on hHsp60 structure related to the function and chemical-physical properties of the substituted amino acids (see text). ²N.R., none reported.