TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35288	106087;106088;106089	chr2:178530753;178530752;178530751	chr2:179395480;179395479;179395478
N2AB	33647	101164;101165;101166	chr2:178530753;178530752;178530751	chr2:179395480;179395479;179395478
N2A	32720	98383;98384;98385	chr2:178530753;178530752;178530751	chr2:179395480;179395479;179395478
N2B	26223	78892;78893;78894	chr2:178530753;178530752;178530751	chr2:179395480;179395479;179395478
Novex-1	26348	79267;79268;79269	chr2:178530753;178530752;178530751	chr2:179395480;179395479;179395478
Novex-2	26415	79468;79469;79470	chr2:178530753;178530752;178530751	chr2:179395480;179395479;179395478
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-165
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.1723
• 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	rs764713884	-2.351	0.322	N	0.495	0.25	0.45553875121	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.77E-05	0
I/T	rs764713884	-2.351	0.322	N	0.495	0.25	0.45553875121	gnomAD-4.0.0	6.8415E-06	None	None	None	None	N	None	2.98704E-05	0	None	0	0	None	0	0	8.09462E-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	0.7773	likely_pathogenic	0.7911	pathogenic	-1.832	Destabilizing	0.115	N	0.433	neutral	None	None	None	None	N
I/C	0.8958	likely_pathogenic	0.9174	pathogenic	-1.066	Destabilizing	0.981	D	0.547	neutral	None	None	None	None	N
I/D	0.9386	likely_pathogenic	0.9403	pathogenic	-1.238	Destabilizing	0.817	D	0.605	neutral	None	None	None	None	N
I/E	0.8869	likely_pathogenic	0.8857	pathogenic	-1.147	Destabilizing	0.817	D	0.604	neutral	None	None	None	None	N
I/F	0.2435	likely_benign	0.2936	benign	-1.076	Destabilizing	0.624	D	0.531	neutral	N	0.403344276	None	None	N
I/G	0.9155	likely_pathogenic	0.9213	pathogenic	-2.251	Highly Destabilizing	0.001	N	0.437	neutral	None	None	None	None	N
I/H	0.8675	likely_pathogenic	0.8822	pathogenic	-1.533	Destabilizing	0.981	D	0.619	neutral	None	None	None	None	N
I/K	0.7899	likely_pathogenic	0.8076	pathogenic	-1.217	Destabilizing	0.817	D	0.607	neutral	None	None	None	None	N
I/L	0.2021	likely_benign	0.2202	benign	-0.705	Destabilizing	0.041	N	0.359	neutral	N	0.493888923	None	None	N
I/M	0.1382	likely_benign	0.1478	benign	-0.579	Destabilizing	0.624	D	0.527	neutral	N	0.467833844	None	None	N
I/N	0.6017	likely_pathogenic	0.5969	pathogenic	-1.15	Destabilizing	0.771	D	0.615	neutral	N	0.468594312	None	None	N
I/P	0.844	likely_pathogenic	0.884	pathogenic	-1.051	Destabilizing	0.932	D	0.619	neutral	None	None	None	None	N
I/Q	0.8218	likely_pathogenic	0.8395	pathogenic	-1.195	Destabilizing	0.932	D	0.612	neutral	None	None	None	None	N
I/R	0.7275	likely_pathogenic	0.7533	pathogenic	-0.792	Destabilizing	0.817	D	0.62	neutral	None	None	None	None	N
I/S	0.7566	likely_pathogenic	0.7635	pathogenic	-1.861	Destabilizing	0.322	N	0.539	neutral	N	0.468087333	None	None	N
I/T	0.7515	likely_pathogenic	0.7635	pathogenic	-1.641	Destabilizing	0.322	N	0.495	neutral	N	0.456477538	None	None	N
I/V	0.1647	likely_benign	0.1738	benign	-1.051	Destabilizing	0.001	N	0.232	neutral	N	0.481108839	None	None	N
I/W	0.8866	likely_pathogenic	0.912	pathogenic	-1.264	Destabilizing	0.981	D	0.651	neutral	None	None	None	None	N
I/Y	0.687	likely_pathogenic	0.7116	pathogenic	-0.998	Destabilizing	0.817	D	0.557	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.