TABLE 1.

Pathogenic LN domain mutations.

Protein	Mutation	Effect	Phenotype	References
LMα1	Y265C	LN interaction	[mouse] Retinal vasculopathy	Edwards et al., 2010
LMα2	C79R	LM poly/foldc	[mouse] mild muscular dystrophy	Patton et al., 2008
	C86Y	foldp	MDC1A	Oliveira et al., 2018
	Y138H	LM polyp	MDC1A	Oliveira et al., 2008
	W152G	foldp	Limb-girdle–type dystrophy	Gavassini et al., 2011
	S157F	foldp	MDC1A	Geranmayeh et al., 2010
	Q167P	LM polyc	Limb-girdle–type dystrophy	Di Blasi et al., 2005
	S204F	foldp	Mild muscular dystrophy, mild proximal weakness	Chan et al., 2014
	L243P	foldp	Mild MDC1A	Gavassini et al., 2011
	S277L	foldp	MDC1A	Beytia Mde et al., 2014
	G284R	LM polyp	limb-girdle–type dystrophy	Gavassini et al., 2011
LMα5	R286L	LM polyc	Focal segmental glomerulosclerosis, hearing loss, craniofacial dysmorphism, limb development	Jones et al., 2020
LMβ1	E215K	LM polyc	[fly] heart development defects	Hollfelder et al., 2014
	V226E		[fly] heart development defects	Hollfelder et al., 2014
	G286R		[fly] heart development defects	Hollfelder et al., 2014
LMβ2	R246W R246Q	LM Secretion/Fold	End-stage renal disease, nephrotic proteinuria, diffuse mesangial sclerosis, focal and segmental glomerulosclerosis, microcoria, lens abnormalities, nystagmus hypotonia, cognitive defects, muscle delay	Zenker et al., 2004; Hasselbacher et al., 2006; Bredrup et al., 2008; Matejas et al., 2010
	V79del	LM polyp	Retinal detachment, cataracts, progressive vision loss, diffuse mesangial sclerosis, end-stage renal disease	Matejas et al., 2006
	S80R	LM polyc	Nephrotic proteinuria, atypical diffuse mesangial sclerosis, myopia, retinal detachment. [mouse S83R] Detrimental on Alport syndrome background	Matejas et al., 2010; Funk et al., 2018
	H147R	LM foldp	Nephrotic proteinuria, diffuse mesangial sclerosis, proliferative glomerulonephritis, hypertension, heart failure, microcoria, retinal detachment, lens abnormalities	Mohney et al., 2011
	D167Y	LM Secretionp	End-stage renal disease, myopia, retinal detachment, severe visual impairment	Kagan et al., 2008
	L139P	LM foldp	Diffuse mesangial sclerosis, lens abnormalities, severe visual impairment, hypotonia, muscle delay, cognitive deficits	Matejas et al., 2010
	S179F	LM foldp	End-stage renal disease, focal and segmented glomerulosclerosis, retinal detachment, severe visual impairments	Choi et al., 2008
LMβ3	E210K	Splicingc + foldp	Skin fragility, nail dystrophy, alopecia	Mellerio et al., 1998

^ppredicted ^cconfirmed in vitro assays.