TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21594	65005;65006;65007	chr2:178584861;178584860;178584859	chr2:179449588;179449587;179449586
N2AB	19953	60082;60083;60084	chr2:178584861;178584860;178584859	chr2:179449588;179449587;179449586
N2A	19026	57301;57302;57303	chr2:178584861;178584860;178584859	chr2:179449588;179449587;179449586
N2B	12529	37810;37811;37812	chr2:178584861;178584860;178584859	chr2:179449588;179449587;179449586
Novex-1	12654	38185;38186;38187	chr2:178584861;178584860;178584859	chr2:179449588;179449587;179449586
Novex-2	12721	38386;38387;38388	chr2:178584861;178584860;178584859	chr2:179449588;179449587;179449586
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: Fn3-44
• Domain position: 36
• Structural Position: 37
• Q(SASA): 0.1527
• 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
N/K	None	None	0.919	N	0.56	0.138	0.18995819373	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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
N/A	0.781	likely_pathogenic	0.8102	pathogenic	-1.127	Destabilizing	0.938	D	0.713	prob.delet.	None	None	None	None	N
N/C	0.5302	ambiguous	0.5436	ambiguous	-0.41	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
N/D	0.7931	likely_pathogenic	0.8369	pathogenic	-1.332	Destabilizing	0.958	D	0.516	neutral	N	0.473672962	None	None	N
N/E	0.9776	likely_pathogenic	0.9823	pathogenic	-1.198	Destabilizing	0.938	D	0.504	neutral	None	None	None	None	N
N/F	0.9772	likely_pathogenic	0.9787	pathogenic	-0.886	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
N/G	0.565	likely_pathogenic	0.61	pathogenic	-1.471	Destabilizing	0.968	D	0.49	neutral	None	None	None	None	N
N/H	0.4339	ambiguous	0.4743	ambiguous	-1.061	Destabilizing	0.994	D	0.695	prob.neutral	D	0.524348768	None	None	N
N/I	0.9759	likely_pathogenic	0.9818	pathogenic	-0.238	Destabilizing	0.994	D	0.897	deleterious	N	0.487853651	None	None	N
N/K	0.9656	likely_pathogenic	0.9722	pathogenic	-0.327	Destabilizing	0.919	D	0.56	neutral	N	0.512187548	None	None	N
N/L	0.9231	likely_pathogenic	0.9405	pathogenic	-0.238	Destabilizing	0.991	D	0.813	deleterious	None	None	None	None	N
N/M	0.9556	likely_pathogenic	0.9663	pathogenic	0.24	Stabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
N/P	0.9964	likely_pathogenic	0.996	pathogenic	-0.507	Destabilizing	0.995	D	0.859	deleterious	None	None	None	None	N
N/Q	0.9175	likely_pathogenic	0.9342	pathogenic	-1.14	Destabilizing	0.484	N	0.42	neutral	None	None	None	None	N
N/R	0.919	likely_pathogenic	0.9293	pathogenic	-0.258	Destabilizing	0.982	D	0.671	neutral	None	None	None	None	N
N/S	0.1695	likely_benign	0.1962	benign	-1.154	Destabilizing	0.958	D	0.505	neutral	N	0.505992294	None	None	N
N/T	0.7779	likely_pathogenic	0.8097	pathogenic	-0.832	Destabilizing	0.958	D	0.585	neutral	N	0.465684019	None	None	N
N/V	0.9456	likely_pathogenic	0.958	pathogenic	-0.507	Destabilizing	0.991	D	0.864	deleterious	None	None	None	None	N
N/W	0.9886	likely_pathogenic	0.9906	pathogenic	-0.616	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
N/Y	0.7752	likely_pathogenic	0.7925	pathogenic	-0.37	Destabilizing	0.998	D	0.865	deleterious	N	0.471622274	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.