TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17634	53125;53126;53127	chr2:178607887;178607886;178607885	chr2:179472614;179472613;179472612
N2AB	15993	48202;48203;48204	chr2:178607887;178607886;178607885	chr2:179472614;179472613;179472612
N2A	15066	45421;45422;45423	chr2:178607887;178607886;178607885	chr2:179472614;179472613;179472612
N2B	8569	25930;25931;25932	chr2:178607887;178607886;178607885	chr2:179472614;179472613;179472612
Novex-1	8694	26305;26306;26307	chr2:178607887;178607886;178607885	chr2:179472614;179472613;179472612
Novex-2	8761	26506;26507;26508	chr2:178607887;178607886;178607885	chr2:179472614;179472613;179472612
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-16
• Domain position: 66
• Structural Position: 97
• Q(SASA): 0.0993
• 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
I/M	rs1219503783	-1.014	0.901	N	0.729	0.221	0.427368086475	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
I/M	rs1219503783	-1.014	0.901	N	0.729	0.221	0.427368086475	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
I/M	rs1219503783	-1.014	0.901	N	0.729	0.221	0.427368086475	gnomAD-4.0.0	6.58181E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47215E-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
I/A	0.808	likely_pathogenic	0.6795	pathogenic	-2.233	Highly Destabilizing	0.415	N	0.755	deleterious	None	None	None	None	N
I/C	0.873	likely_pathogenic	0.7695	pathogenic	-1.32	Destabilizing	0.996	D	0.812	deleterious	None	None	None	None	N
I/D	0.9854	likely_pathogenic	0.968	pathogenic	-2.16	Highly Destabilizing	0.987	D	0.876	deleterious	None	None	None	None	N
I/E	0.9653	likely_pathogenic	0.943	pathogenic	-2.062	Highly Destabilizing	0.961	D	0.868	deleterious	None	None	None	None	N
I/F	0.6238	likely_pathogenic	0.465	ambiguous	-1.439	Destabilizing	0.901	D	0.729	prob.delet.	N	0.442637036	None	None	N
I/G	0.9378	likely_pathogenic	0.8733	pathogenic	-2.662	Highly Destabilizing	0.961	D	0.854	deleterious	None	None	None	None	N
I/H	0.9761	likely_pathogenic	0.9497	pathogenic	-1.944	Destabilizing	0.996	D	0.88	deleterious	None	None	None	None	N
I/K	0.9479	likely_pathogenic	0.9158	pathogenic	-1.769	Destabilizing	0.961	D	0.872	deleterious	None	None	None	None	N
I/L	0.1707	likely_benign	0.1326	benign	-1.06	Destabilizing	0.19	N	0.538	neutral	N	0.222504833	None	None	N
I/M	0.1956	likely_benign	0.1462	benign	-0.781	Destabilizing	0.901	D	0.729	prob.delet.	N	0.391458854	None	None	N
I/N	0.8367	likely_pathogenic	0.7345	pathogenic	-1.734	Destabilizing	0.983	D	0.884	deleterious	N	0.472959943	None	None	N
I/P	0.9605	likely_pathogenic	0.9235	pathogenic	-1.425	Destabilizing	0.987	D	0.885	deleterious	None	None	None	None	N
I/Q	0.9506	likely_pathogenic	0.9142	pathogenic	-1.805	Destabilizing	0.987	D	0.876	deleterious	None	None	None	None	N
I/R	0.9378	likely_pathogenic	0.8934	pathogenic	-1.209	Destabilizing	0.961	D	0.883	deleterious	None	None	None	None	N
I/S	0.8647	likely_pathogenic	0.7561	pathogenic	-2.352	Highly Destabilizing	0.901	D	0.828	deleterious	N	0.472786584	None	None	N
I/T	0.7738	likely_pathogenic	0.6224	pathogenic	-2.13	Highly Destabilizing	0.722	D	0.771	deleterious	N	0.453931465	None	None	N
I/V	0.1123	likely_benign	0.0944	benign	-1.425	Destabilizing	0.001	N	0.389	neutral	N	0.352497821	None	None	N
I/W	0.9843	likely_pathogenic	0.9629	pathogenic	-1.673	Destabilizing	0.996	D	0.866	deleterious	None	None	None	None	N
I/Y	0.9319	likely_pathogenic	0.877	pathogenic	-1.436	Destabilizing	0.961	D	0.816	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.