TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31579	94960;94961;94962	chr2:178546693;178546692;178546691	chr2:179411420;179411419;179411418
N2AB	29938	90037;90038;90039	chr2:178546693;178546692;178546691	chr2:179411420;179411419;179411418
N2A	29011	87256;87257;87258	chr2:178546693;178546692;178546691	chr2:179411420;179411419;179411418
N2B	22514	67765;67766;67767	chr2:178546693;178546692;178546691	chr2:179411420;179411419;179411418
Novex-1	22639	68140;68141;68142	chr2:178546693;178546692;178546691	chr2:179411420;179411419;179411418
Novex-2	22706	68341;68342;68343	chr2:178546693;178546692;178546691	chr2:179411420;179411419;179411418
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-118
• Domain position: 74
• Structural Position: 103
• Q(SASA): 0.1413
• 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
T/A	rs1252165343	-1.242	0.005	N	0.137	0.128	0.115124310173	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	9.81E-05	None	0	0	0
T/A	rs1252165343	-1.242	0.005	N	0.137	0.128	0.115124310173	gnomAD-4.0.0	2.73691E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99499E-07	3.47818E-05	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
T/A	0.0773	likely_benign	0.0711	benign	-0.943	Destabilizing	0.005	N	0.137	neutral	N	0.463204309	None	None	N
T/C	0.3707	ambiguous	0.3673	ambiguous	-0.597	Destabilizing	0.998	D	0.535	neutral	None	None	None	None	N
T/D	0.3742	ambiguous	0.3746	ambiguous	-0.645	Destabilizing	0.728	D	0.483	neutral	None	None	None	None	N
T/E	0.256	likely_benign	0.2658	benign	-0.575	Destabilizing	0.016	N	0.261	neutral	None	None	None	None	N
T/F	0.3228	likely_benign	0.3019	benign	-0.783	Destabilizing	0.949	D	0.581	neutral	None	None	None	None	N
T/G	0.2418	likely_benign	0.2259	benign	-1.276	Destabilizing	0.728	D	0.499	neutral	None	None	None	None	N
T/H	0.2801	likely_benign	0.2702	benign	-1.549	Destabilizing	0.974	D	0.59	neutral	None	None	None	None	N
T/I	0.1368	likely_benign	0.1317	benign	-0.121	Destabilizing	0.669	D	0.511	neutral	N	0.49477801	None	None	N
T/K	0.1937	likely_benign	0.2008	benign	-0.788	Destabilizing	0.728	D	0.465	neutral	None	None	None	None	N
T/L	0.1116	likely_benign	0.1069	benign	-0.121	Destabilizing	0.525	D	0.398	neutral	None	None	None	None	N
T/M	0.0998	likely_benign	0.0943	benign	0.093	Stabilizing	0.325	N	0.322	neutral	None	None	None	None	N
T/N	0.1325	likely_benign	0.1308	benign	-0.954	Destabilizing	0.801	D	0.527	neutral	N	0.459739929	None	None	N
T/P	0.2412	likely_benign	0.1975	benign	-0.362	Destabilizing	0.891	D	0.544	neutral	N	0.477384328	None	None	N
T/Q	0.204	likely_benign	0.2038	benign	-0.989	Destabilizing	0.172	N	0.311	neutral	None	None	None	None	N
T/R	0.1595	likely_benign	0.1617	benign	-0.707	Destabilizing	0.842	D	0.512	neutral	None	None	None	None	N
T/S	0.1033	likely_benign	0.0997	benign	-1.212	Destabilizing	0.454	N	0.414	neutral	N	0.425416712	None	None	N
T/V	0.1084	likely_benign	0.1047	benign	-0.362	Destabilizing	0.525	D	0.405	neutral	None	None	None	None	N
T/W	0.706	likely_pathogenic	0.6813	pathogenic	-0.782	Destabilizing	0.998	D	0.609	neutral	None	None	None	None	N
T/Y	0.3278	likely_benign	0.3185	benign	-0.516	Destabilizing	0.991	D	0.583	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.