TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30001	90226;90227;90228	chr2:178552899;178552898;178552897	chr2:179417626;179417625;179417624
N2AB	28360	85303;85304;85305	chr2:178552899;178552898;178552897	chr2:179417626;179417625;179417624
N2A	27433	82522;82523;82524	chr2:178552899;178552898;178552897	chr2:179417626;179417625;179417624
N2B	20936	63031;63032;63033	chr2:178552899;178552898;178552897	chr2:179417626;179417625;179417624
Novex-1	21061	63406;63407;63408	chr2:178552899;178552898;178552897	chr2:179417626;179417625;179417624
Novex-2	21128	63607;63608;63609	chr2:178552899;178552898;178552897	chr2:179417626;179417625;179417624
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: Fn3-106
• Domain position: 69
• Structural Position: 102
• Q(SASA): 0.1538
• 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	None	None	None	N	0.165	0.089	0.236890367714	gnomAD-4.0.0	6.84213E-07	None	None	None	None	N	None	0	0	None	3.82643E-05	0	None	0	0	0	0	0
T/N	None	None	0.741	N	0.494	0.236	0.294918367191	gnomAD-4.0.0	2.05264E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69837E-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	0.0943	likely_benign	0.0937	benign	-0.939	Destabilizing	0.052	N	0.355	neutral	N	0.451878168	None	None	N
T/C	0.3918	ambiguous	0.3652	ambiguous	-0.434	Destabilizing	0.935	D	0.443	neutral	None	None	None	None	N
T/D	0.4269	ambiguous	0.4312	ambiguous	-0.221	Destabilizing	0.555	D	0.482	neutral	None	None	None	None	N
T/E	0.2929	likely_benign	0.3024	benign	-0.19	Destabilizing	0.555	D	0.463	neutral	None	None	None	None	N
T/F	0.2353	likely_benign	0.2156	benign	-0.835	Destabilizing	0.38	N	0.469	neutral	None	None	None	None	N
T/G	0.3418	ambiguous	0.3348	benign	-1.239	Destabilizing	0.262	N	0.425	neutral	None	None	None	None	N
T/H	0.2656	likely_benign	0.2519	benign	-1.42	Destabilizing	0.935	D	0.431	neutral	None	None	None	None	N
T/I	0.0909	likely_benign	0.0827	benign	-0.214	Destabilizing	None	N	0.165	neutral	N	0.514582853	None	None	N
T/K	0.2517	likely_benign	0.251	benign	-0.775	Destabilizing	0.555	D	0.46	neutral	None	None	None	None	N
T/L	0.0867	likely_benign	0.078	benign	-0.214	Destabilizing	0.005	N	0.375	neutral	None	None	None	None	N
T/M	0.0748	likely_benign	0.0704	benign	0.067	Stabilizing	0.38	N	0.471	neutral	None	None	None	None	N
T/N	0.1065	likely_benign	0.1027	benign	-0.747	Destabilizing	0.741	D	0.494	neutral	N	0.490263198	None	None	N
T/P	0.2937	likely_benign	0.3132	benign	-0.423	Destabilizing	0.741	D	0.477	neutral	N	0.509171727	None	None	N
T/Q	0.222	likely_benign	0.2149	benign	-0.836	Destabilizing	0.791	D	0.481	neutral	None	None	None	None	N
T/R	0.2498	likely_benign	0.2397	benign	-0.585	Destabilizing	0.555	D	0.475	neutral	None	None	None	None	N
T/S	0.1218	likely_benign	0.1192	benign	-1.062	Destabilizing	0.211	N	0.417	neutral	N	0.468674418	None	None	N
T/V	0.0919	likely_benign	0.0877	benign	-0.423	Destabilizing	0.001	N	0.084	neutral	None	None	None	None	N
T/W	0.6421	likely_pathogenic	0.642	pathogenic	-0.78	Destabilizing	0.935	D	0.463	neutral	None	None	None	None	N
T/Y	0.2495	likely_benign	0.2441	benign	-0.563	Destabilizing	0.555	D	0.473	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.