TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17981	54166;54167;54168	chr2:178605236;178605235;178605234	chr2:179469963;179469962;179469961
N2AB	16340	49243;49244;49245	chr2:178605236;178605235;178605234	chr2:179469963;179469962;179469961
N2A	15413	46462;46463;46464	chr2:178605236;178605235;178605234	chr2:179469963;179469962;179469961
N2B	8916	26971;26972;26973	chr2:178605236;178605235;178605234	chr2:179469963;179469962;179469961
Novex-1	9041	27346;27347;27348	chr2:178605236;178605235;178605234	chr2:179469963;179469962;179469961
Novex-2	9108	27547;27548;27549	chr2:178605236;178605235;178605234	chr2:179469963;179469962;179469961
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-114
• Domain position: 14
• Structural Position: 24
• Q(SASA): 0.3462
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
G/E	None	None	0.998	D	0.702	0.732	0.658189440816	gnomAD-4.0.0	1.59961E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.44063E-05	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
G/A	0.4911	ambiguous	0.4498	ambiguous	-0.576	Destabilizing	0.996	D	0.672	neutral	D	0.593180233	None	None	N
G/C	0.6934	likely_pathogenic	0.6604	pathogenic	-0.89	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
G/D	0.4439	ambiguous	0.3594	ambiguous	-1.162	Destabilizing	0.996	D	0.74	deleterious	None	None	None	None	N
G/E	0.5945	likely_pathogenic	0.501	ambiguous	-1.306	Destabilizing	0.998	D	0.702	prob.neutral	D	0.575516078	None	None	N
G/F	0.9219	likely_pathogenic	0.9018	pathogenic	-1.141	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
G/H	0.7614	likely_pathogenic	0.696	pathogenic	-0.957	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
G/I	0.9344	likely_pathogenic	0.9156	pathogenic	-0.559	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
G/K	0.7871	likely_pathogenic	0.7066	pathogenic	-1.306	Destabilizing	0.998	D	0.708	prob.delet.	None	None	None	None	N
G/L	0.835	likely_pathogenic	0.7954	pathogenic	-0.559	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
G/M	0.8503	likely_pathogenic	0.819	pathogenic	-0.45	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
G/N	0.3653	ambiguous	0.3297	benign	-0.873	Destabilizing	0.683	D	0.441	neutral	None	None	None	None	N
G/P	0.9943	likely_pathogenic	0.9927	pathogenic	-0.529	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
G/Q	0.6564	likely_pathogenic	0.574	pathogenic	-1.183	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
G/R	0.7065	likely_pathogenic	0.6122	pathogenic	-0.773	Destabilizing	0.999	D	0.742	deleterious	D	0.614509021	None	None	N
G/S	0.2353	likely_benign	0.2096	benign	-0.986	Destabilizing	0.994	D	0.718	prob.delet.	None	None	None	None	N
G/T	0.5814	likely_pathogenic	0.5449	ambiguous	-1.075	Destabilizing	0.998	D	0.703	prob.neutral	None	None	None	None	N
G/V	0.8674	likely_pathogenic	0.837	pathogenic	-0.529	Destabilizing	1.0	D	0.724	prob.delet.	D	0.614710825	None	None	N
G/W	0.871	likely_pathogenic	0.822	pathogenic	-1.345	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
G/Y	0.8584	likely_pathogenic	0.8171	pathogenic	-1.022	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.