TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9033	27322;27323;27324	chr2:178712928;178712927;178712926	chr2:179577655;179577654;179577653
N2AB	8716	26371;26372;26373	chr2:178712928;178712927;178712926	chr2:179577655;179577654;179577653
N2A	7789	23590;23591;23592	chr2:178712928;178712927;178712926	chr2:179577655;179577654;179577653
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Ig-76
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.3072
• 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	1.0	D	0.773	0.715	0.876181674074	gnomAD-4.0.0	1.59319E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86102E-06	0	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	0.2889	likely_benign	0.3339	benign	-0.337	Destabilizing	0.997	D	0.667	neutral	D	0.620343497	None	None	N
G/C	0.5401	ambiguous	0.5954	pathogenic	-0.863	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
G/D	0.2622	likely_benign	0.3106	benign	-0.701	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
G/E	0.3136	likely_benign	0.4059	ambiguous	-0.87	Destabilizing	1.0	D	0.773	deleterious	D	0.597571719	None	None	N
G/F	0.8254	likely_pathogenic	0.8721	pathogenic	-1.121	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
G/H	0.5153	ambiguous	0.5657	pathogenic	-0.604	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
G/I	0.776	likely_pathogenic	0.8617	pathogenic	-0.482	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
G/K	0.4548	ambiguous	0.5483	ambiguous	-0.802	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
G/L	0.7535	likely_pathogenic	0.8109	pathogenic	-0.482	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
G/M	0.7623	likely_pathogenic	0.8241	pathogenic	-0.4	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
G/N	0.3377	likely_benign	0.3635	ambiguous	-0.459	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
G/P	0.9504	likely_pathogenic	0.9668	pathogenic	-0.401	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
G/Q	0.4216	ambiguous	0.493	ambiguous	-0.781	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
G/R	0.3285	likely_benign	0.4182	ambiguous	-0.334	Destabilizing	1.0	D	0.791	deleterious	D	0.630064052	None	None	N
G/S	0.1618	likely_benign	0.1763	benign	-0.59	Destabilizing	0.986	D	0.579	neutral	None	None	None	None	N
G/T	0.4166	ambiguous	0.4772	ambiguous	-0.694	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
G/V	0.6296	likely_pathogenic	0.7369	pathogenic	-0.401	Destabilizing	1.0	D	0.782	deleterious	D	0.636766467	None	None	N
G/W	0.676	likely_pathogenic	0.7714	pathogenic	-1.26	Destabilizing	1.0	D	0.773	deleterious	D	0.646487022	None	None	N
G/Y	0.6841	likely_pathogenic	0.7549	pathogenic	-0.908	Destabilizing	1.0	D	0.802	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.