TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2185	6778;6779;6780	chr2:178775158;178775157;178775156	chr2:179639885;179639884;179639883
N2AB	2185	6778;6779;6780	chr2:178775158;178775157;178775156	chr2:179639885;179639884;179639883
N2A	2185	6778;6779;6780	chr2:178775158;178775157;178775156	chr2:179639885;179639884;179639883
N2B	2139	6640;6641;6642	chr2:178775158;178775157;178775156	chr2:179639885;179639884;179639883
Novex-1	2139	6640;6641;6642	chr2:178775158;178775157;178775156	chr2:179639885;179639884;179639883
Novex-2	2139	6640;6641;6642	chr2:178775158;178775157;178775156	chr2:179639885;179639884;179639883
Novex-3	2185	6778;6779;6780	chr2:178775158;178775157;178775156	chr2:179639885;179639884;179639883

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-11
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.1644
• 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
A/P	rs367653049	-1.049	1.0	D	0.745	0.772	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
A/P	rs367653049	-1.049	1.0	D	0.745	0.772	None	gnomAD-4.0.0	6.57462E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46998E-05	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
A/C	0.6147	likely_pathogenic	0.6234	pathogenic	-0.932	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
A/D	0.9567	likely_pathogenic	0.9612	pathogenic	-1.711	Destabilizing	1.0	D	0.724	prob.delet.	D	0.697308112	None	None	N
A/E	0.91	likely_pathogenic	0.9201	pathogenic	-1.713	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
A/F	0.8404	likely_pathogenic	0.85	pathogenic	-1.028	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
A/G	0.3235	likely_benign	0.329	benign	-1.349	Destabilizing	0.999	D	0.54	neutral	D	0.594125917	None	None	N
A/H	0.953	likely_pathogenic	0.9565	pathogenic	-1.603	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
A/I	0.573	likely_pathogenic	0.59	pathogenic	-0.422	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
A/K	0.9603	likely_pathogenic	0.965	pathogenic	-1.567	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
A/L	0.5153	ambiguous	0.533	ambiguous	-0.422	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
A/M	0.6497	likely_pathogenic	0.6615	pathogenic	-0.309	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
A/N	0.9059	likely_pathogenic	0.9153	pathogenic	-1.306	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
A/P	0.975	likely_pathogenic	0.9765	pathogenic	-0.595	Destabilizing	1.0	D	0.745	deleterious	D	0.69656033	None	None	N
A/Q	0.8807	likely_pathogenic	0.8944	pathogenic	-1.436	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
A/R	0.9188	likely_pathogenic	0.9259	pathogenic	-1.182	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
A/S	0.214	likely_benign	0.2215	benign	-1.601	Destabilizing	0.999	D	0.575	neutral	D	0.568586227	None	None	N
A/T	0.2191	likely_benign	0.2314	benign	-1.521	Destabilizing	1.0	D	0.72	prob.delet.	N	0.512700378	None	None	N
A/V	0.2601	likely_benign	0.2724	benign	-0.595	Destabilizing	0.999	D	0.639	neutral	N	0.486237427	None	None	N
A/W	0.9841	likely_pathogenic	0.9847	pathogenic	-1.467	Destabilizing	1.0	D	0.65	neutral	None	None	None	None	N
A/Y	0.9387	likely_pathogenic	0.9436	pathogenic	-1.069	Destabilizing	1.0	D	0.713	prob.delet.	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.