TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16870	50833;50834;50835	chr2:178611621;178611620;178611619	chr2:179476348;179476347;179476346
N2AB	15229	45910;45911;45912	chr2:178611621;178611620;178611619	chr2:179476348;179476347;179476346
N2A	14302	43129;43130;43131	chr2:178611621;178611620;178611619	chr2:179476348;179476347;179476346
N2B	7805	23638;23639;23640	chr2:178611621;178611620;178611619	chr2:179476348;179476347;179476346
Novex-1	7930	24013;24014;24015	chr2:178611621;178611620;178611619	chr2:179476348;179476347;179476346
Novex-2	7997	24214;24215;24216	chr2:178611621;178611620;178611619	chr2:179476348;179476347;179476346
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-11
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.1373
• 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
A/T	None	None	0.379	N	0.563	0.146	0.269111216191	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	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
A/C	0.4313	ambiguous	0.5082	ambiguous	-1.236	Destabilizing	0.005	N	0.414	neutral	None	None	None	None	N
A/D	0.3555	ambiguous	0.3454	ambiguous	-2.535	Highly Destabilizing	0.004	N	0.509	neutral	N	0.436390056	None	None	N
A/E	0.4062	ambiguous	0.421	ambiguous	-2.454	Highly Destabilizing	0.447	N	0.621	neutral	None	None	None	None	N
A/F	0.4493	ambiguous	0.4951	ambiguous	-1.083	Destabilizing	0.972	D	0.693	prob.neutral	None	None	None	None	N
A/G	0.2173	likely_benign	0.2308	benign	-1.635	Destabilizing	0.201	N	0.525	neutral	N	0.468948375	None	None	N
A/H	0.5921	likely_pathogenic	0.6124	pathogenic	-2.077	Highly Destabilizing	0.992	D	0.655	neutral	None	None	None	None	N
A/I	0.3424	ambiguous	0.399	ambiguous	-0.308	Destabilizing	0.85	D	0.716	prob.delet.	None	None	None	None	N
A/K	0.7904	likely_pathogenic	0.8068	pathogenic	-1.719	Destabilizing	0.617	D	0.659	neutral	None	None	None	None	N
A/L	0.257	likely_benign	0.2859	benign	-0.308	Destabilizing	0.447	N	0.629	neutral	None	None	None	None	N
A/M	0.2827	likely_benign	0.3158	benign	-0.231	Destabilizing	0.992	D	0.655	neutral	None	None	None	None	N
A/N	0.2619	likely_benign	0.2778	benign	-1.7	Destabilizing	0.447	N	0.694	prob.neutral	None	None	None	None	N
A/P	0.9449	likely_pathogenic	0.9447	pathogenic	-0.583	Destabilizing	0.896	D	0.715	prob.delet.	N	0.479681287	None	None	N
A/Q	0.469	ambiguous	0.4887	ambiguous	-1.703	Destabilizing	0.85	D	0.711	prob.delet.	None	None	None	None	N
A/R	0.7058	likely_pathogenic	0.7235	pathogenic	-1.483	Destabilizing	0.85	D	0.705	prob.neutral	None	None	None	None	N
A/S	0.084	likely_benign	0.0849	benign	-2.005	Highly Destabilizing	0.007	N	0.243	neutral	N	0.42776826	None	None	N
A/T	0.0946	likely_benign	0.0977	benign	-1.83	Destabilizing	0.379	N	0.563	neutral	N	0.36331042	None	None	N
A/V	0.1666	likely_benign	0.1904	benign	-0.583	Destabilizing	0.549	D	0.577	neutral	N	0.428759168	None	None	N
A/W	0.8772	likely_pathogenic	0.8911	pathogenic	-1.744	Destabilizing	0.992	D	0.725	prob.delet.	None	None	None	None	N
A/Y	0.6257	likely_pathogenic	0.655	pathogenic	-1.284	Destabilizing	0.972	D	0.667	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.