TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3413	10462;10463;10464	chr2:178759050;178759049;178759048	chr2:179623777;179623776;179623775
N2AB	3413	10462;10463;10464	chr2:178759050;178759049;178759048	chr2:179623777;179623776;179623775
N2A	3413	10462;10463;10464	chr2:178759050;178759049;178759048	chr2:179623777;179623776;179623775
N2B	3367	10324;10325;10326	chr2:178759050;178759049;178759048	chr2:179623777;179623776;179623775
Novex-1	3367	10324;10325;10326	chr2:178759050;178759049;178759048	chr2:179623777;179623776;179623775
Novex-2	3367	10324;10325;10326	chr2:178759050;178759049;178759048	chr2:179623777;179623776;179623775
Novex-3	3413	10462;10463;10464	chr2:178759050;178759049;178759048	chr2:179623777;179623776;179623775

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-24
• Domain position: 69
• Structural Position: 153
• Q(SASA): 0.3796
• 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/P	None	None	0.266	D	0.505	0.253	0.328752806141	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-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	0.0764	likely_benign	0.0761	benign	-1.189	Destabilizing	0.005	N	0.269	neutral	D	0.531405233	None	None	N
T/C	0.3566	ambiguous	0.3011	benign	-0.791	Destabilizing	0.356	N	0.5	neutral	None	None	None	None	N
T/D	0.2477	likely_benign	0.2652	benign	-0.668	Destabilizing	0.016	N	0.421	neutral	None	None	None	None	N
T/E	0.1867	likely_benign	0.1993	benign	-0.66	Destabilizing	None	N	0.203	neutral	None	None	None	None	N
T/F	0.1409	likely_benign	0.1331	benign	-1.444	Destabilizing	0.214	N	0.594	neutral	None	None	None	None	N
T/G	0.2251	likely_benign	0.2254	benign	-1.419	Destabilizing	0.136	N	0.461	neutral	None	None	None	None	N
T/H	0.1865	likely_benign	0.1795	benign	-1.726	Destabilizing	0.356	N	0.537	neutral	None	None	None	None	N
T/I	0.0613	likely_benign	0.0518	benign	-0.657	Destabilizing	None	N	0.207	neutral	N	0.510952412	None	None	N
T/K	0.1282	likely_benign	0.1381	benign	-0.748	Destabilizing	0.016	N	0.421	neutral	None	None	None	None	N
T/L	0.0597	likely_benign	0.0527	benign	-0.657	Destabilizing	0.002	N	0.309	neutral	None	None	None	None	N
T/M	0.0761	likely_benign	0.0707	benign	-0.169	Destabilizing	0.214	N	0.519	neutral	None	None	None	None	N
T/N	0.0872	likely_benign	0.0884	benign	-0.769	Destabilizing	0.106	N	0.34	neutral	N	0.511607447	None	None	N
T/P	0.1122	likely_benign	0.1011	benign	-0.806	Destabilizing	0.266	N	0.505	neutral	D	0.585233177	None	None	N
T/Q	0.159	likely_benign	0.1667	benign	-1.036	Destabilizing	0.003	N	0.267	neutral	None	None	None	None	N
T/R	0.1002	likely_benign	0.1042	benign	-0.479	Destabilizing	0.072	N	0.429	neutral	None	None	None	None	N
T/S	0.0998	likely_benign	0.1019	benign	-1.073	Destabilizing	0.024	N	0.347	neutral	N	0.508140706	None	None	N
T/V	0.0723	likely_benign	0.0689	benign	-0.806	Destabilizing	None	N	0.167	neutral	None	None	None	None	N
T/W	0.4616	ambiguous	0.4338	ambiguous	-1.313	Destabilizing	0.864	D	0.543	neutral	None	None	None	None	N
T/Y	0.226	likely_benign	0.2057	benign	-1.066	Destabilizing	0.356	N	0.591	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.