TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26252	78979;78980;78981	chr2:178567378;178567377;178567376	chr2:179432105;179432104;179432103
N2AB	24611	74056;74057;74058	chr2:178567378;178567377;178567376	chr2:179432105;179432104;179432103
N2A	23684	71275;71276;71277	chr2:178567378;178567377;178567376	chr2:179432105;179432104;179432103
N2B	17187	51784;51785;51786	chr2:178567378;178567377;178567376	chr2:179432105;179432104;179432103
Novex-1	17312	52159;52160;52161	chr2:178567378;178567377;178567376	chr2:179432105;179432104;179432103
Novex-2	17379	52360;52361;52362	chr2:178567378;178567377;178567376	chr2:179432105;179432104;179432103
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-137
• Domain position: 60
• Structural Position: 139
• Q(SASA): 0.1554
• 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
I/T	None	None	0.013	N	0.313	0.183	0.617987307765	gnomAD-4.0.0	4.85157E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.33639E-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
I/A	0.2069	likely_benign	0.1988	benign	-2.801	Highly Destabilizing	0.103	N	0.42	neutral	None	None	None	None	N
I/C	0.5761	likely_pathogenic	0.5554	ambiguous	-1.972	Destabilizing	0.965	D	0.57	neutral	None	None	None	None	N
I/D	0.6754	likely_pathogenic	0.7026	pathogenic	-3.195	Highly Destabilizing	0.561	D	0.599	neutral	None	None	None	None	N
I/E	0.5243	ambiguous	0.5458	ambiguous	-2.987	Highly Destabilizing	0.561	D	0.561	neutral	None	None	None	None	N
I/F	0.1523	likely_benign	0.1463	benign	-1.612	Destabilizing	0.772	D	0.555	neutral	D	0.531115317	None	None	N
I/G	0.6239	likely_pathogenic	0.5989	pathogenic	-3.308	Highly Destabilizing	0.39	N	0.541	neutral	None	None	None	None	N
I/H	0.3975	ambiguous	0.4028	ambiguous	-2.672	Highly Destabilizing	0.991	D	0.609	neutral	None	None	None	None	N
I/K	0.4326	ambiguous	0.4535	ambiguous	-2.193	Highly Destabilizing	0.561	D	0.559	neutral	None	None	None	None	N
I/L	0.1087	likely_benign	0.106	benign	-1.325	Destabilizing	0.001	N	0.199	neutral	N	0.465583758	None	None	N
I/M	0.0886	likely_benign	0.0873	benign	-1.28	Destabilizing	0.772	D	0.57	neutral	N	0.515300503	None	None	N
I/N	0.2621	likely_benign	0.268	benign	-2.48	Highly Destabilizing	0.772	D	0.599	neutral	N	0.497965536	None	None	N
I/P	0.9281	likely_pathogenic	0.9254	pathogenic	-1.801	Destabilizing	0.901	D	0.597	neutral	None	None	None	None	N
I/Q	0.4113	ambiguous	0.4163	ambiguous	-2.379	Highly Destabilizing	0.901	D	0.602	neutral	None	None	None	None	N
I/R	0.3191	likely_benign	0.3359	benign	-1.794	Destabilizing	0.818	D	0.602	neutral	None	None	None	None	N
I/S	0.1895	likely_benign	0.1888	benign	-3.124	Highly Destabilizing	0.013	N	0.434	neutral	N	0.472491088	None	None	N
I/T	0.0841	likely_benign	0.086	benign	-2.792	Highly Destabilizing	0.013	N	0.313	neutral	N	0.429774887	None	None	N
I/V	0.0671	likely_benign	0.0654	benign	-1.801	Destabilizing	None	N	0.195	neutral	N	0.430759109	None	None	N
I/W	0.6839	likely_pathogenic	0.6589	pathogenic	-2.006	Highly Destabilizing	0.991	D	0.631	neutral	None	None	None	None	N
I/Y	0.4573	ambiguous	0.454	ambiguous	-1.793	Destabilizing	0.901	D	0.567	neutral	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.