TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7439	22540;22541;22542	chr2:178722472;178722471;178722470	chr2:179587199;179587198;179587197
N2AB	7122	21589;21590;21591	chr2:178722472;178722471;178722470	chr2:179587199;179587198;179587197
N2A	6195	18808;18809;18810	chr2:178722472;178722471;178722470	chr2:179587199;179587198;179587197
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-59
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.4152
• 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
T/I	rs2078562379	None	0.27	N	0.427	0.228	0.606262950116	gnomAD-4.0.0	1.59206E-06	None	None	None	None	N	None	0	0	None	0	2.77331E-05	None	0	0	0	0	0
T/P	rs772268509	-0.549	0.784	N	0.445	0.29	0.645914728649	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
T/P	rs772268509	-0.549	0.784	N	0.445	0.29	0.645914728649	gnomAD-4.0.0	1.36871E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79929E-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
T/A	0.0875	likely_benign	0.0903	benign	-1.021	Destabilizing	0.139	N	0.297	neutral	N	0.490519488	None	None	N
T/C	0.5249	ambiguous	0.5216	ambiguous	-0.63	Destabilizing	0.995	D	0.473	neutral	None	None	None	None	N
T/D	0.3141	likely_benign	0.3089	benign	-0.256	Destabilizing	0.001	N	0.284	neutral	None	None	None	None	N
T/E	0.2561	likely_benign	0.2542	benign	-0.215	Destabilizing	0.004	N	0.281	neutral	None	None	None	None	N
T/F	0.2426	likely_benign	0.2445	benign	-0.96	Destabilizing	0.893	D	0.581	neutral	None	None	None	None	N
T/G	0.2761	likely_benign	0.293	benign	-1.321	Destabilizing	0.495	N	0.436	neutral	None	None	None	None	N
T/H	0.2318	likely_benign	0.2389	benign	-1.519	Destabilizing	0.981	D	0.511	neutral	None	None	None	None	N
T/I	0.1721	likely_benign	0.1789	benign	-0.295	Destabilizing	0.27	N	0.427	neutral	N	0.515071216	None	None	N
T/K	0.2522	likely_benign	0.2799	benign	-0.72	Destabilizing	0.495	N	0.415	neutral	None	None	None	None	N
T/L	0.1222	likely_benign	0.122	benign	-0.295	Destabilizing	0.144	N	0.389	neutral	None	None	None	None	N
T/M	0.0983	likely_benign	0.1003	benign	-0.059	Destabilizing	0.085	N	0.36	neutral	None	None	None	None	N
T/N	0.1096	likely_benign	0.1152	benign	-0.764	Destabilizing	0.473	N	0.355	neutral	N	0.485785672	None	None	N
T/P	0.2198	likely_benign	0.2263	benign	-0.504	Destabilizing	0.784	D	0.445	neutral	N	0.503680787	None	None	N
T/Q	0.1996	likely_benign	0.2136	benign	-0.864	Destabilizing	0.704	D	0.462	neutral	None	None	None	None	N
T/R	0.2018	likely_benign	0.2166	benign	-0.559	Destabilizing	0.704	D	0.487	neutral	None	None	None	None	N
T/S	0.0955	likely_benign	0.1024	benign	-1.104	Destabilizing	0.425	N	0.363	neutral	N	0.455078763	None	None	N
T/V	0.1463	likely_benign	0.1541	benign	-0.504	Destabilizing	0.003	N	0.23	neutral	None	None	None	None	N
T/W	0.5959	likely_pathogenic	0.5804	pathogenic	-0.87	Destabilizing	0.995	D	0.532	neutral	None	None	None	None	N
T/Y	0.2722	likely_benign	0.2676	benign	-0.636	Destabilizing	0.944	D	0.548	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.