TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30148	90667;90668;90669	chr2:178552458;178552457;178552456	chr2:179417185;179417184;179417183
N2AB	28507	85744;85745;85746	chr2:178552458;178552457;178552456	chr2:179417185;179417184;179417183
N2A	27580	82963;82964;82965	chr2:178552458;178552457;178552456	chr2:179417185;179417184;179417183
N2B	21083	63472;63473;63474	chr2:178552458;178552457;178552456	chr2:179417185;179417184;179417183
Novex-1	21208	63847;63848;63849	chr2:178552458;178552457;178552456	chr2:179417185;179417184;179417183
Novex-2	21275	64048;64049;64050	chr2:178552458;178552457;178552456	chr2:179417185;179417184;179417183
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-148
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.5108
• 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
N/S	rs1699818097	None	0.999	N	0.545	0.353	0.193865811164	gnomAD-4.0.0	3.20853E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.89133E-06	0	3.04692E-05

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
N/A	0.3605	ambiguous	0.2742	benign	-0.627	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	I
N/C	0.4119	ambiguous	0.3341	benign	0.371	Stabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
N/D	0.2741	likely_benign	0.1924	benign	-0.27	Destabilizing	0.999	D	0.591	neutral	N	0.463710449	None	None	I
N/E	0.7729	likely_pathogenic	0.6324	pathogenic	-0.232	Destabilizing	0.999	D	0.692	prob.neutral	None	None	None	None	I
N/F	0.7874	likely_pathogenic	0.7119	pathogenic	-0.622	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
N/G	0.414	ambiguous	0.3428	ambiguous	-0.914	Destabilizing	0.999	D	0.558	neutral	None	None	None	None	I
N/H	0.1795	likely_benign	0.1511	benign	-0.9	Destabilizing	1.0	D	0.656	neutral	N	0.510312318	None	None	I
N/I	0.4795	ambiguous	0.3663	ambiguous	0.076	Stabilizing	1.0	D	0.749	deleterious	N	0.480975619	None	None	I
N/K	0.7049	likely_pathogenic	0.559	ambiguous	-0.175	Destabilizing	1.0	D	0.699	prob.neutral	N	0.473543441	None	None	I
N/L	0.4196	ambiguous	0.3345	benign	0.076	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
N/M	0.5582	ambiguous	0.4562	ambiguous	0.639	Stabilizing	1.0	D	0.671	neutral	None	None	None	None	I
N/P	0.5137	ambiguous	0.4052	ambiguous	-0.129	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	I
N/Q	0.607	likely_pathogenic	0.5091	ambiguous	-0.622	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
N/R	0.6698	likely_pathogenic	0.5513	ambiguous	-0.204	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
N/S	0.1052	likely_benign	0.092	benign	-0.523	Destabilizing	0.999	D	0.545	neutral	N	0.424055983	None	None	I
N/T	0.1804	likely_benign	0.1403	benign	-0.313	Destabilizing	0.999	D	0.689	prob.neutral	N	0.409683963	None	None	I
N/V	0.4365	ambiguous	0.3347	benign	-0.129	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
N/W	0.9213	likely_pathogenic	0.8786	pathogenic	-0.489	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
N/Y	0.3733	ambiguous	0.2994	benign	-0.281	Destabilizing	1.0	D	0.71	prob.delet.	N	0.481229109	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.