TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1162	3709;3710;3711	chr2:178781160;178781159;178781158	chr2:179645887;179645886;179645885
N2AB	1162	3709;3710;3711	chr2:178781160;178781159;178781158	chr2:179645887;179645886;179645885
N2A	1162	3709;3710;3711	chr2:178781160;178781159;178781158	chr2:179645887;179645886;179645885
N2B	1116	3571;3572;3573	chr2:178781160;178781159;178781158	chr2:179645887;179645886;179645885
Novex-1	1116	3571;3572;3573	chr2:178781160;178781159;178781158	chr2:179645887;179645886;179645885
Novex-2	1116	3571;3572;3573	chr2:178781160;178781159;178781158	chr2:179645887;179645886;179645885
Novex-3	1162	3709;3710;3711	chr2:178781160;178781159;178781158	chr2:179645887;179645886;179645885

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-4
• Domain position: 81
• Structural Position: 163
• Q(SASA): 0.9933
• Predicted PPI site: I

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
H/R	rs146887683	0.219	0.006	N	0.319	0.107	None	gnomAD-2.1.1	3.98E-06	None	None	None	None	I	None	6.15E-05	0	None	0	0	None	0	None	0	0	0
H/R	rs146887683	0.219	0.006	N	0.319	0.107	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
H/R	rs146887683	0.219	0.006	N	0.319	0.107	None	gnomAD-4.0.0	2.47837E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.38993E-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
H/A	0.4704	ambiguous	0.5041	ambiguous	0.488	Stabilizing	0.495	N	0.545	neutral	None	None	None	None	I
H/C	0.3243	likely_benign	0.326	benign	0.754	Stabilizing	0.995	D	0.525	neutral	None	None	None	None	I
H/D	0.4565	ambiguous	0.4615	ambiguous	-0.18	Destabilizing	0.642	D	0.493	neutral	D	0.581653883	None	None	I
H/E	0.4813	ambiguous	0.4823	ambiguous	-0.172	Destabilizing	0.543	D	0.371	neutral	None	None	None	None	I
H/F	0.1933	likely_benign	0.2079	benign	1.017	Stabilizing	0.007	N	0.399	neutral	None	None	None	None	I
H/G	0.5959	likely_pathogenic	0.6576	pathogenic	0.247	Stabilizing	0.828	D	0.539	neutral	None	None	None	None	I
H/I	0.3873	ambiguous	0.411	ambiguous	1.087	Stabilizing	0.543	D	0.545	neutral	None	None	None	None	I
H/K	0.5294	ambiguous	0.5449	ambiguous	0.377	Stabilizing	0.543	D	0.464	neutral	None	None	None	None	I
H/L	0.1307	likely_benign	0.1384	benign	1.087	Stabilizing	0.006	N	0.416	neutral	N	0.472642579	None	None	I
H/M	0.5284	ambiguous	0.548	ambiguous	0.78	Stabilizing	0.893	D	0.555	neutral	None	None	None	None	I
H/N	0.1625	likely_benign	0.1725	benign	0.307	Stabilizing	0.642	D	0.389	neutral	N	0.508397071	None	None	I
H/P	0.8495	likely_pathogenic	0.8694	pathogenic	0.912	Stabilizing	0.975	D	0.559	neutral	D	0.581653883	None	None	I
H/Q	0.3209	likely_benign	0.3452	ambiguous	0.377	Stabilizing	0.065	N	0.297	neutral	N	0.502252575	None	None	I
H/R	0.2634	likely_benign	0.2766	benign	-0.18	Destabilizing	0.006	N	0.319	neutral	N	0.508397071	None	None	I
H/S	0.4209	ambiguous	0.4512	ambiguous	0.481	Stabilizing	0.704	D	0.489	neutral	None	None	None	None	I
H/T	0.518	ambiguous	0.5474	ambiguous	0.582	Stabilizing	0.828	D	0.535	neutral	None	None	None	None	I
H/V	0.3439	ambiguous	0.365	ambiguous	0.912	Stabilizing	0.543	D	0.555	neutral	None	None	None	None	I
H/W	0.3665	ambiguous	0.387	ambiguous	0.907	Stabilizing	0.985	D	0.547	neutral	None	None	None	None	I
H/Y	0.0674	likely_benign	0.0694	benign	1.201	Stabilizing	0.006	N	0.279	neutral	N	0.456845499	None	None	I

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.