TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6333	19222;19223;19224	chr2:178729041;178729040;178729039	chr2:179593768;179593767;179593766
N2AB	6016	18271;18272;18273	chr2:178729041;178729040;178729039	chr2:179593768;179593767;179593766
N2A	5089	15490;15491;15492	chr2:178729041;178729040;178729039	chr2:179593768;179593767;179593766
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-47
• Domain position: 42
• Structural Position: 59
• Q(SASA): 0.8268
• 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
D/Y	rs1275885460	0.21	0.741	N	0.364	0.237	0.467161347466	gnomAD-2.1.1	4.06E-06	None	None	None	None	I	None	0	2.92E-05	None	0	0	None	0	None	0	0	0
D/Y	rs1275885460	0.21	0.741	N	0.364	0.237	0.467161347466	gnomAD-4.0.0	1.59366E-06	None	None	None	None	I	None	0	2.2941E-05	None	0	0	None	0	0	0	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
D/A	0.075	likely_benign	0.0731	benign	0.116	Stabilizing	0.001	N	0.196	neutral	N	0.441840107	None	None	I
D/C	0.2771	likely_benign	0.2738	benign	-0.195	Destabilizing	0.935	D	0.353	neutral	None	None	None	None	I
D/E	0.0702	likely_benign	0.0708	benign	-0.273	Destabilizing	None	N	0.17	neutral	N	0.415904299	None	None	I
D/F	0.2608	likely_benign	0.2408	benign	0.163	Stabilizing	0.791	D	0.365	neutral	None	None	None	None	I
D/G	0.0819	likely_benign	0.0746	benign	-0.032	Destabilizing	0.027	N	0.387	neutral	N	0.424467855	None	None	I
D/H	0.0994	likely_benign	0.0953	benign	0.776	Stabilizing	0.317	N	0.345	neutral	N	0.460292582	None	None	I
D/I	0.1315	likely_benign	0.1297	benign	0.443	Stabilizing	0.555	D	0.371	neutral	None	None	None	None	I
D/K	0.0894	likely_benign	0.0835	benign	0.492	Stabilizing	0.035	N	0.374	neutral	None	None	None	None	I
D/L	0.1282	likely_benign	0.1232	benign	0.443	Stabilizing	0.149	N	0.395	neutral	None	None	None	None	I
D/M	0.2412	likely_benign	0.236	benign	0.142	Stabilizing	0.935	D	0.342	neutral	None	None	None	None	I
D/N	0.0696	likely_benign	0.0674	benign	0.076	Stabilizing	None	N	0.173	neutral	N	0.445725774	None	None	I
D/P	0.2649	likely_benign	0.223	benign	0.355	Stabilizing	0.262	N	0.381	neutral	None	None	None	None	I
D/Q	0.0982	likely_benign	0.0938	benign	0.123	Stabilizing	0.081	N	0.334	neutral	None	None	None	None	I
D/R	0.1084	likely_benign	0.0989	benign	0.781	Stabilizing	0.081	N	0.361	neutral	None	None	None	None	I
D/S	0.0723	likely_benign	0.0711	benign	0.012	Stabilizing	0.035	N	0.357	neutral	None	None	None	None	I
D/T	0.0953	likely_benign	0.0938	benign	0.144	Stabilizing	0.149	N	0.375	neutral	None	None	None	None	I
D/V	0.0817	likely_benign	0.0831	benign	0.355	Stabilizing	0.117	N	0.393	neutral	N	0.440533385	None	None	I
D/W	0.5297	ambiguous	0.4819	ambiguous	0.224	Stabilizing	0.935	D	0.446	neutral	None	None	None	None	I
D/Y	0.1114	likely_benign	0.1037	benign	0.4	Stabilizing	0.741	D	0.364	neutral	N	0.493135719	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.