TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27350	82273;82274;82275	chr2:178564084;178564083;178564082	chr2:179428811;179428810;179428809
N2AB	25709	77350;77351;77352	chr2:178564084;178564083;178564082	chr2:179428811;179428810;179428809
N2A	24782	74569;74570;74571	chr2:178564084;178564083;178564082	chr2:179428811;179428810;179428809
N2B	18285	55078;55079;55080	chr2:178564084;178564083;178564082	chr2:179428811;179428810;179428809
Novex-1	18410	55453;55454;55455	chr2:178564084;178564083;178564082	chr2:179428811;179428810;179428809
Novex-2	18477	55654;55655;55656	chr2:178564084;178564083;178564082	chr2:179428811;179428810;179428809
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-140
• Domain position: 73
• Structural Position: 157
• Q(SASA): 0.4178
• 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
K/Q	None	None	0.007	N	0.324	0.142	0.206339911435	gnomAD-4.0.0	1.59125E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85843E-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
K/A	0.2358	likely_benign	0.2879	benign	-0.675	Destabilizing	0.129	N	0.467	neutral	None	None	None	None	N
K/C	0.3949	ambiguous	0.4514	ambiguous	-0.881	Destabilizing	0.983	D	0.579	neutral	None	None	None	None	N
K/D	0.4527	ambiguous	0.509	ambiguous	-0.079	Destabilizing	0.129	N	0.482	neutral	None	None	None	None	N
K/E	0.1419	likely_benign	0.1639	benign	0.017	Stabilizing	0.007	N	0.257	neutral	N	0.482342722	None	None	N
K/F	0.5098	ambiguous	0.6226	pathogenic	-0.571	Destabilizing	0.716	D	0.601	neutral	None	None	None	None	N
K/G	0.3861	ambiguous	0.4598	ambiguous	-1.004	Destabilizing	0.129	N	0.535	neutral	None	None	None	None	N
K/H	0.134	likely_benign	0.1466	benign	-1.362	Destabilizing	0.836	D	0.584	neutral	None	None	None	None	N
K/I	0.1799	likely_benign	0.2259	benign	0.165	Stabilizing	0.004	N	0.535	neutral	N	0.4674907	None	None	N
K/L	0.1818	likely_benign	0.2389	benign	0.165	Stabilizing	0.049	N	0.533	neutral	None	None	None	None	N
K/M	0.1172	likely_benign	0.1447	benign	0.084	Stabilizing	0.716	D	0.581	neutral	None	None	None	None	N
K/N	0.2022	likely_benign	0.2445	benign	-0.406	Destabilizing	0.001	N	0.259	neutral	N	0.513377705	None	None	N
K/P	0.9186	likely_pathogenic	0.948	pathogenic	-0.086	Destabilizing	0.593	D	0.611	neutral	None	None	None	None	N
K/Q	0.0819	likely_benign	0.0874	benign	-0.581	Destabilizing	0.007	N	0.324	neutral	N	0.484438878	None	None	N
K/R	0.0756	likely_benign	0.0793	benign	-0.482	Destabilizing	0.213	N	0.473	neutral	N	0.47345388	None	None	N
K/S	0.212	likely_benign	0.2573	benign	-1.158	Destabilizing	0.027	N	0.255	neutral	None	None	None	None	N
K/T	0.0731	likely_benign	0.0871	benign	-0.861	Destabilizing	0.213	N	0.503	neutral	N	0.428489595	None	None	N
K/V	0.1777	likely_benign	0.2208	benign	-0.086	Destabilizing	0.11	N	0.557	neutral	None	None	None	None	N
K/W	0.5519	ambiguous	0.6386	pathogenic	-0.389	Destabilizing	0.983	D	0.601	neutral	None	None	None	None	N
K/Y	0.3492	ambiguous	0.4182	ambiguous	-0.051	Destabilizing	0.836	D	0.615	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.