TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19003	57232;57233;57234	chr2:178598610;178598609;178598608	chr2:179463337;179463336;179463335
N2AB	17362	52309;52310;52311	chr2:178598610;178598609;178598608	chr2:179463337;179463336;179463335
N2A	16435	49528;49529;49530	chr2:178598610;178598609;178598608	chr2:179463337;179463336;179463335
N2B	9938	30037;30038;30039	chr2:178598610;178598609;178598608	chr2:179463337;179463336;179463335
Novex-1	10063	30412;30413;30414	chr2:178598610;178598609;178598608	chr2:179463337;179463336;179463335
Novex-2	10130	30613;30614;30615	chr2:178598610;178598609;178598608	chr2:179463337;179463336;179463335
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-26
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.3398
• 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
S/A	rs2052418644	None	0.543	N	0.186	0.165	0.226586394389	gnomAD-4.0.0	1.6053E-06	None	None	None	None	N	None	0	0	None	0	2.79158E-05	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
S/A	0.1263	likely_benign	0.1297	benign	-0.597	Destabilizing	0.543	D	0.186	neutral	N	0.47153705	None	None	N
S/C	0.1381	likely_benign	0.1331	benign	-0.418	Destabilizing	1.0	D	0.613	neutral	None	None	None	None	N
S/D	0.3845	ambiguous	0.4364	ambiguous	-0.815	Destabilizing	0.996	D	0.54	neutral	None	None	None	None	N
S/E	0.5194	ambiguous	0.5443	ambiguous	-0.859	Destabilizing	0.996	D	0.537	neutral	None	None	None	None	N
S/F	0.207	likely_benign	0.2191	benign	-1.069	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
S/G	0.1427	likely_benign	0.1451	benign	-0.781	Destabilizing	0.992	D	0.42	neutral	None	None	None	None	N
S/H	0.3042	likely_benign	0.3167	benign	-1.38	Destabilizing	1.0	D	0.611	neutral	None	None	None	None	N
S/I	0.3058	likely_benign	0.3115	benign	-0.223	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
S/K	0.6484	likely_pathogenic	0.6452	pathogenic	-0.712	Destabilizing	0.996	D	0.531	neutral	None	None	None	None	N
S/L	0.1462	likely_benign	0.1453	benign	-0.223	Destabilizing	0.989	D	0.585	neutral	N	0.506277529	None	None	N
S/M	0.2023	likely_benign	0.209	benign	0.311	Stabilizing	1.0	D	0.615	neutral	None	None	None	None	N
S/N	0.1369	likely_benign	0.144	benign	-0.671	Destabilizing	1.0	D	0.557	neutral	None	None	None	None	N
S/P	0.9529	likely_pathogenic	0.9512	pathogenic	-0.317	Destabilizing	0.998	D	0.639	neutral	N	0.506531019	None	None	N
S/Q	0.4776	ambiguous	0.4844	ambiguous	-0.984	Destabilizing	1.0	D	0.618	neutral	None	None	None	None	N
S/R	0.6342	likely_pathogenic	0.6233	pathogenic	-0.459	Destabilizing	0.999	D	0.643	neutral	None	None	None	None	N
S/T	0.0655	likely_benign	0.0706	benign	-0.648	Destabilizing	0.989	D	0.419	neutral	N	0.426798005	None	None	N
S/V	0.2912	likely_benign	0.2988	benign	-0.317	Destabilizing	0.998	D	0.613	neutral	None	None	None	None	N
S/W	0.4186	ambiguous	0.4351	ambiguous	-1.06	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
S/Y	0.1849	likely_benign	0.1839	benign	-0.771	Destabilizing	1.0	D	0.7	prob.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.