TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17300	52123;52124;52125	chr2:178609412;178609411;178609410	chr2:179474139;179474138;179474137
N2AB	15659	47200;47201;47202	chr2:178609412;178609411;178609410	chr2:179474139;179474138;179474137
N2A	14732	44419;44420;44421	chr2:178609412;178609411;178609410	chr2:179474139;179474138;179474137
N2B	8235	24928;24929;24930	chr2:178609412;178609411;178609410	chr2:179474139;179474138;179474137
Novex-1	8360	25303;25304;25305	chr2:178609412;178609411;178609410	chr2:179474139;179474138;179474137
Novex-2	8427	25504;25505;25506	chr2:178609412;178609411;178609410	chr2:179474139;179474138;179474137
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-112
• Domain position: 50
• Structural Position: 82
• Q(SASA): 0.0903
• 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
L/F	rs760140429	-1.621	0.029	N	0.547	0.036	0.0762999501168	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	5.82E-05	None	0	0	None	0	None	0	0	0
L/F	rs760140429	-1.621	0.029	N	0.547	0.036	0.0762999501168	gnomAD-4.0.0	3.18918E-06	None	None	None	None	N	None	0	2.2899E-05	None	0	0	None	0	0	0	0	3.03251E-05

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
L/A	0.0671	likely_benign	0.0694	benign	-0.489	Destabilizing	0.016	N	0.391	neutral	None	None	None	None	N
L/C	0.2337	likely_benign	0.254	benign	-0.834	Destabilizing	0.676	D	0.529	neutral	None	None	None	None	N
L/D	0.2398	likely_benign	0.2396	benign	-0.383	Destabilizing	0.214	N	0.587	neutral	None	None	None	None	N
L/E	0.1256	likely_benign	0.1262	benign	-0.473	Destabilizing	0.072	N	0.545	neutral	None	None	None	None	N
L/F	0.0883	likely_benign	0.0866	benign	-0.751	Destabilizing	0.029	N	0.547	neutral	N	0.465580971	None	None	N
L/G	0.1569	likely_benign	0.1669	benign	-0.555	Destabilizing	0.072	N	0.533	neutral	None	None	None	None	N
L/H	0.1023	likely_benign	0.11	benign	-0.01	Destabilizing	0.214	N	0.561	neutral	None	None	None	None	N
L/I	0.0613	likely_benign	0.0623	benign	-0.426	Destabilizing	None	N	0.189	neutral	None	None	None	None	N
L/K	0.0915	likely_benign	0.0981	benign	-0.42	Destabilizing	0.038	N	0.499	neutral	None	None	None	None	N
L/M	0.087	likely_benign	0.0895	benign	-0.747	Destabilizing	0.005	N	0.289	neutral	N	0.465580971	None	None	N
L/N	0.12	likely_benign	0.1226	benign	-0.28	Destabilizing	0.214	N	0.586	neutral	None	None	None	None	N
L/P	0.0565	likely_benign	0.0616	benign	-0.424	Destabilizing	0.001	N	0.433	neutral	None	None	None	None	N
L/Q	0.0746	likely_benign	0.079	benign	-0.442	Destabilizing	0.214	N	0.559	neutral	None	None	None	None	N
L/R	0.081	likely_benign	0.0864	benign	-0.014	Destabilizing	0.001	N	0.401	neutral	None	None	None	None	N
L/S	0.0837	likely_benign	0.0884	benign	-0.611	Destabilizing	0.029	N	0.505	neutral	N	0.465060896	None	None	N
L/T	0.074	likely_benign	0.0739	benign	-0.613	Destabilizing	None	N	0.343	neutral	None	None	None	None	N
L/V	0.0572	likely_benign	0.0599	benign	-0.424	Destabilizing	None	N	0.234	neutral	N	0.404241724	None	None	N
L/W	0.1531	likely_benign	0.1581	benign	-0.772	Destabilizing	0.612	D	0.575	neutral	N	0.466274405	None	None	N
L/Y	0.171	likely_benign	0.1809	benign	-0.554	Destabilizing	0.001	N	0.331	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.