TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22662	68209;68210;68211	chr2:178579046;178579045;178579044	chr2:179443773;179443772;179443771
N2AB	21021	63286;63287;63288	chr2:178579046;178579045;178579044	chr2:179443773;179443772;179443771
N2A	20094	60505;60506;60507	chr2:178579046;178579045;178579044	chr2:179443773;179443772;179443771
N2B	13597	41014;41015;41016	chr2:178579046;178579045;178579044	chr2:179443773;179443772;179443771
Novex-1	13722	41389;41390;41391	chr2:178579046;178579045;178579044	chr2:179443773;179443772;179443771
Novex-2	13789	41590;41591;41592	chr2:178579046;178579045;178579044	chr2:179443773;179443772;179443771
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-52
• Domain position: 20
• Structural Position: 21
• Q(SASA): 0.1508
• 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/P	rs1484148632	None	1.0	N	0.695	0.616	0.478828542108	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/P	rs1484148632	None	1.0	N	0.695	0.616	0.478828542108	gnomAD-4.0.0	6.57566E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47119E-05	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
T/A	0.1882	likely_benign	0.146	benign	-0.977	Destabilizing	0.999	D	0.548	neutral	N	0.514326563	None	None	N
T/C	0.4709	ambiguous	0.3996	ambiguous	-1.106	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
T/D	0.7349	likely_pathogenic	0.6375	pathogenic	-2.032	Highly Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
T/E	0.6317	likely_pathogenic	0.5361	ambiguous	-1.893	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
T/F	0.3664	ambiguous	0.274	benign	-0.646	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
T/G	0.5173	ambiguous	0.4335	ambiguous	-1.329	Destabilizing	1.0	D	0.646	neutral	None	None	None	None	N
T/H	0.4083	ambiguous	0.3363	benign	-1.505	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
T/I	0.178	likely_benign	0.1271	benign	-0.082	Destabilizing	1.0	D	0.683	prob.neutral	N	0.499954543	None	None	N
T/K	0.5282	ambiguous	0.4243	ambiguous	-1.02	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
T/L	0.1251	likely_benign	0.101	benign	-0.082	Destabilizing	0.999	D	0.624	neutral	None	None	None	None	N
T/M	0.0966	likely_benign	0.0857	benign	-0.096	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
T/N	0.2011	likely_benign	0.16	benign	-1.587	Destabilizing	1.0	D	0.645	neutral	N	0.476372442	None	None	N
T/P	0.7853	likely_pathogenic	0.6649	pathogenic	-0.349	Destabilizing	1.0	D	0.695	prob.neutral	N	0.502732357	None	None	N
T/Q	0.4294	ambiguous	0.3555	ambiguous	-1.517	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
T/R	0.4949	ambiguous	0.3831	ambiguous	-0.985	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
T/S	0.1905	likely_benign	0.1689	benign	-1.652	Destabilizing	0.999	D	0.543	neutral	N	0.510784825	None	None	N
T/V	0.1459	likely_benign	0.113	benign	-0.349	Destabilizing	0.999	D	0.569	neutral	None	None	None	None	N
T/W	0.7493	likely_pathogenic	0.6721	pathogenic	-0.83	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
T/Y	0.4158	ambiguous	0.3289	benign	-0.477	Destabilizing	1.0	D	0.761	deleterious	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.