TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29402	88429;88430;88431	chr2:178556950;178556949;178556948	chr2:179421677;179421676;179421675
N2AB	27761	83506;83507;83508	chr2:178556950;178556949;178556948	chr2:179421677;179421676;179421675
N2A	26834	80725;80726;80727	chr2:178556950;178556949;178556948	chr2:179421677;179421676;179421675
N2B	20337	61234;61235;61236	chr2:178556950;178556949;178556948	chr2:179421677;179421676;179421675
Novex-1	20462	61609;61610;61611	chr2:178556950;178556949;178556948	chr2:179421677;179421676;179421675
Novex-2	20529	61810;61811;61812	chr2:178556950;178556949;178556948	chr2:179421677;179421676;179421675
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Fn3-102
• Domain position: 68
• Structural Position: 99
• Q(SASA): 0.5098
• 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
Q/E	None	None	0.953	N	0.463	0.219	0.185906805712	gnomAD-4.0.0	1.5913E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-05	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
Q/A	0.2759	likely_benign	0.2326	benign	-0.282	Destabilizing	0.985	D	0.407	neutral	None	None	None	None	N
Q/C	0.8834	likely_pathogenic	0.8368	pathogenic	0.346	Stabilizing	1.0	D	0.602	neutral	None	None	None	None	N
Q/D	0.6891	likely_pathogenic	0.578	pathogenic	-0.49	Destabilizing	0.993	D	0.476	neutral	None	None	None	None	N
Q/E	0.0851	likely_benign	0.0731	benign	-0.509	Destabilizing	0.953	D	0.463	neutral	N	0.315227512	None	None	N
Q/F	0.9342	likely_pathogenic	0.8995	pathogenic	-0.469	Destabilizing	0.999	D	0.567	neutral	None	None	None	None	N
Q/G	0.4254	ambiguous	0.3509	ambiguous	-0.506	Destabilizing	0.993	D	0.453	neutral	None	None	None	None	N
Q/H	0.5724	likely_pathogenic	0.4577	ambiguous	-0.609	Destabilizing	0.999	D	0.433	neutral	N	0.477480328	None	None	N
Q/I	0.6522	likely_pathogenic	0.581	pathogenic	0.23	Stabilizing	0.999	D	0.559	neutral	None	None	None	None	N
Q/K	0.2118	likely_benign	0.1531	benign	0.007	Stabilizing	0.4	N	0.141	neutral	N	0.454083394	None	None	N
Q/L	0.3558	ambiguous	0.3005	benign	0.23	Stabilizing	0.99	D	0.453	neutral	N	0.47030364	None	None	N
Q/M	0.5802	likely_pathogenic	0.5316	ambiguous	0.786	Stabilizing	0.999	D	0.433	neutral	None	None	None	None	N
Q/N	0.531	ambiguous	0.4545	ambiguous	-0.298	Destabilizing	0.993	D	0.445	neutral	None	None	None	None	N
Q/P	0.1332	likely_benign	0.1086	benign	0.089	Stabilizing	0.999	D	0.397	neutral	N	0.33074039	None	None	N
Q/R	0.2357	likely_benign	0.1702	benign	0.181	Stabilizing	0.961	D	0.515	neutral	N	0.473362588	None	None	N
Q/S	0.4036	ambiguous	0.3472	ambiguous	-0.287	Destabilizing	0.985	D	0.456	neutral	None	None	None	None	N
Q/T	0.4267	ambiguous	0.3441	ambiguous	-0.151	Destabilizing	0.993	D	0.413	neutral	None	None	None	None	N
Q/V	0.4356	ambiguous	0.3753	ambiguous	0.089	Stabilizing	0.998	D	0.418	neutral	None	None	None	None	N
Q/W	0.8774	likely_pathogenic	0.8034	pathogenic	-0.426	Destabilizing	1.0	D	0.585	neutral	None	None	None	None	N
Q/Y	0.8361	likely_pathogenic	0.7504	pathogenic	-0.162	Destabilizing	0.999	D	0.419	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.