TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7592	22999;23000;23001	chr2:178721889;178721888;178721887	chr2:179586616;179586615;179586614
N2AB	7275	22048;22049;22050	chr2:178721889;178721888;178721887	chr2:179586616;179586615;179586614
N2A	6348	19267;19268;19269	chr2:178721889;178721888;178721887	chr2:179586616;179586615;179586614
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-60
• Domain position: 78
• Structural Position: 162
• Q(SASA): 1.0352
• 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/E	None	None	0.046	N	0.345	0.059	0.17258766438	gnomAD-4.0.0	6.84583E-07	None	None	None	None	I	None	0	0	None	0	2.51953E-05	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	0.1815	likely_benign	0.1817	benign	-0.087	Destabilizing	0.939	D	0.447	neutral	N	0.396395819	None	None	I
D/C	0.7747	likely_pathogenic	0.7679	pathogenic	0.12	Stabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	I
D/E	0.115	likely_benign	0.1172	benign	-0.312	Destabilizing	0.046	N	0.345	neutral	N	0.423675634	None	None	I
D/F	0.6599	likely_pathogenic	0.6696	pathogenic	-0.212	Destabilizing	0.999	D	0.603	neutral	None	None	None	None	I
D/G	0.2389	likely_benign	0.2316	benign	-0.228	Destabilizing	0.939	D	0.441	neutral	N	0.457425635	None	None	I
D/H	0.3629	ambiguous	0.3669	ambiguous	0.103	Stabilizing	0.998	D	0.469	neutral	N	0.492962361	None	None	I
D/I	0.374	ambiguous	0.3803	ambiguous	0.218	Stabilizing	0.993	D	0.609	neutral	None	None	None	None	I
D/K	0.4434	ambiguous	0.4463	ambiguous	0.494	Stabilizing	0.386	N	0.417	neutral	None	None	None	None	I
D/L	0.4357	ambiguous	0.4479	ambiguous	0.218	Stabilizing	0.986	D	0.584	neutral	None	None	None	None	I
D/M	0.6189	likely_pathogenic	0.6306	pathogenic	0.24	Stabilizing	0.999	D	0.63	neutral	None	None	None	None	I
D/N	0.1369	likely_benign	0.1339	benign	0.278	Stabilizing	0.939	D	0.46	neutral	N	0.476011396	None	None	I
D/P	0.7289	likely_pathogenic	0.7504	pathogenic	0.137	Stabilizing	0.993	D	0.463	neutral	None	None	None	None	I
D/Q	0.3649	ambiguous	0.3796	ambiguous	0.276	Stabilizing	0.973	D	0.458	neutral	None	None	None	None	I
D/R	0.4679	ambiguous	0.4757	ambiguous	0.61	Stabilizing	0.973	D	0.47	neutral	None	None	None	None	I
D/S	0.1489	likely_benign	0.1484	benign	0.199	Stabilizing	0.953	D	0.443	neutral	None	None	None	None	I
D/T	0.2636	likely_benign	0.2667	benign	0.306	Stabilizing	0.986	D	0.419	neutral	None	None	None	None	I
D/V	0.2174	likely_benign	0.2214	benign	0.137	Stabilizing	0.991	D	0.584	neutral	N	0.446363279	None	None	I
D/W	0.9143	likely_pathogenic	0.9143	pathogenic	-0.16	Destabilizing	0.999	D	0.706	prob.neutral	None	None	None	None	I
D/Y	0.3253	likely_benign	0.3271	benign	0.013	Stabilizing	0.999	D	0.607	neutral	N	0.500947126	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.