TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7823	23692;23693;23694	chr2:178720175;178720174;178720173	chr2:179584902;179584901;179584900
N2AB	7506	22741;22742;22743	chr2:178720175;178720174;178720173	chr2:179584902;179584901;179584900
N2A	6579	19960;19961;19962	chr2:178720175;178720174;178720173	chr2:179584902;179584901;179584900
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-63
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.7506
• Predicted PPI site: I

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
P/L	rs2154300491	None	1.0	N	0.665	0.518	0.854352048779	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
P/T	rs768540966	-0.134	0.791	N	0.429	0.333	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
P/T	rs768540966	-0.134	0.791	N	0.429	0.333	None	gnomAD-4.0.0	2.1896E-05	None	None	None	None	I	None	0	0	None	0	8.06289E-04	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
P/A	0.5846	likely_pathogenic	0.4729	ambiguous	-0.446	Destabilizing	0.988	D	0.599	neutral	N	0.49259209	None	None	I
P/C	0.9805	likely_pathogenic	0.9675	pathogenic	-0.566	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	I
P/D	0.8565	likely_pathogenic	0.7991	pathogenic	-0.407	Destabilizing	0.995	D	0.669	neutral	None	None	None	None	I
P/E	0.8317	likely_pathogenic	0.7578	pathogenic	-0.538	Destabilizing	0.997	D	0.661	neutral	None	None	None	None	I
P/F	0.9779	likely_pathogenic	0.9631	pathogenic	-0.781	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	I
P/G	0.8457	likely_pathogenic	0.7885	pathogenic	-0.554	Destabilizing	0.999	D	0.627	neutral	None	None	None	None	I
P/H	0.839	likely_pathogenic	0.7732	pathogenic	-0.179	Destabilizing	1.0	D	0.648	neutral	None	None	None	None	I
P/I	0.9352	likely_pathogenic	0.9028	pathogenic	-0.317	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	I
P/K	0.9165	likely_pathogenic	0.8693	pathogenic	-0.412	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	I
P/L	0.7681	likely_pathogenic	0.6766	pathogenic	-0.317	Destabilizing	1.0	D	0.665	neutral	N	0.509241541	None	None	I
P/M	0.9236	likely_pathogenic	0.8801	pathogenic	-0.331	Destabilizing	1.0	D	0.646	neutral	None	None	None	None	I
P/N	0.8314	likely_pathogenic	0.7596	pathogenic	-0.109	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	I
P/Q	0.8043	likely_pathogenic	0.714	pathogenic	-0.39	Destabilizing	1.0	D	0.641	neutral	N	0.493869083	None	None	I
P/R	0.8425	likely_pathogenic	0.7832	pathogenic	0.127	Stabilizing	1.0	D	0.675	prob.neutral	N	0.502493592	None	None	I
P/S	0.7503	likely_pathogenic	0.6408	pathogenic	-0.425	Destabilizing	0.998	D	0.627	neutral	N	0.508481073	None	None	I
P/T	0.6995	likely_pathogenic	0.582	pathogenic	-0.461	Destabilizing	0.791	D	0.429	neutral	N	0.492325374	None	None	I
P/V	0.8537	likely_pathogenic	0.7921	pathogenic	-0.326	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	I
P/W	0.9886	likely_pathogenic	0.9819	pathogenic	-0.849	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	I
P/Y	0.9579	likely_pathogenic	0.9362	pathogenic	-0.547	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	I

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.