TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21753	65482;65483;65484	chr2:178584294;178584293;178584292	chr2:179449021;179449020;179449019
N2AB	20112	60559;60560;60561	chr2:178584294;178584293;178584292	chr2:179449021;179449020;179449019
N2A	19185	57778;57779;57780	chr2:178584294;178584293;178584292	chr2:179449021;179449020;179449019
N2B	12688	38287;38288;38289	chr2:178584294;178584293;178584292	chr2:179449021;179449020;179449019
Novex-1	12813	38662;38663;38664	chr2:178584294;178584293;178584292	chr2:179449021;179449020;179449019
Novex-2	12880	38863;38864;38865	chr2:178584294;178584293;178584292	chr2:179449021;179449020;179449019
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: Fn3-45
• Domain position: 95
• Structural Position: 129
• Q(SASA): 0.3279
• 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	rs748999109	0.021	0.999	N	0.797	0.377	0.541875726618	gnomAD-2.1.1	9.01E-06	None	None	None	None	N	None	0	0	None	0	1.167E-04	None	0	None	0	0	0
T/I	rs748999109	0.021	0.999	N	0.797	0.377	0.541875726618	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.9425E-04	None	0	0	0	0	0
T/I	rs748999109	0.021	0.999	N	0.797	0.377	0.541875726618	gnomAD-4.0.0	4.07279E-06	None	None	None	None	N	None	0	0	None	0	7.3928E-05	None	0	0	0	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	0.1041	likely_benign	0.1026	benign	-0.723	Destabilizing	0.997	D	0.731	deleterious	N	0.487953612	None	None	N
T/C	0.4651	ambiguous	0.4209	ambiguous	-0.511	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
T/D	0.8398	likely_pathogenic	0.7596	pathogenic	-0.07	Destabilizing	0.999	D	0.802	deleterious	None	None	None	None	N
T/E	0.6687	likely_pathogenic	0.5781	pathogenic	-0.079	Destabilizing	0.999	D	0.8	deleterious	None	None	None	None	N
T/F	0.4283	ambiguous	0.3381	benign	-0.828	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
T/G	0.5306	ambiguous	0.4874	ambiguous	-0.968	Destabilizing	0.999	D	0.661	prob.neutral	None	None	None	None	N
T/H	0.5505	ambiguous	0.4663	ambiguous	-1.223	Destabilizing	1.0	D	0.735	deleterious	None	None	None	None	N
T/I	0.2244	likely_benign	0.1803	benign	-0.169	Destabilizing	0.999	D	0.797	deleterious	N	0.490396484	None	None	N
T/K	0.5279	ambiguous	0.4338	ambiguous	-0.67	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
T/L	0.1245	likely_benign	0.1074	benign	-0.169	Destabilizing	0.998	D	0.775	deleterious	None	None	None	None	N
T/M	0.1005	likely_benign	0.0909	benign	0.055	Stabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
T/N	0.3393	likely_benign	0.2853	benign	-0.595	Destabilizing	0.999	D	0.758	deleterious	N	0.492028524	None	None	N
T/P	0.1594	likely_benign	0.1566	benign	-0.321	Destabilizing	0.999	D	0.788	deleterious	N	0.476379804	None	None	N
T/Q	0.4404	ambiguous	0.375	ambiguous	-0.767	Destabilizing	0.999	D	0.808	deleterious	None	None	None	None	N
T/R	0.4505	ambiguous	0.3498	ambiguous	-0.426	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
T/S	0.2472	likely_benign	0.2184	benign	-0.889	Destabilizing	0.997	D	0.768	deleterious	D	0.526645286	None	None	N
T/V	0.1459	likely_benign	0.1254	benign	-0.321	Destabilizing	0.998	D	0.767	deleterious	None	None	None	None	N
T/W	0.7932	likely_pathogenic	0.7047	pathogenic	-0.754	Destabilizing	1.0	D	0.648	neutral	None	None	None	None	N
T/Y	0.4933	ambiguous	0.409	ambiguous	-0.519	Destabilizing	1.0	D	0.783	deleterious	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.