TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33301	100126;100127;100128	chr2:178537208;178537207;178537206	chr2:179401935;179401934;179401933
N2AB	31660	95203;95204;95205	chr2:178537208;178537207;178537206	chr2:179401935;179401934;179401933
N2A	30733	92422;92423;92424	chr2:178537208;178537207;178537206	chr2:179401935;179401934;179401933
N2B	24236	72931;72932;72933	chr2:178537208;178537207;178537206	chr2:179401935;179401934;179401933
Novex-1	24361	73306;73307;73308	chr2:178537208;178537207;178537206	chr2:179401935;179401934;179401933
Novex-2	24428	73507;73508;73509	chr2:178537208;178537207;178537206	chr2:179401935;179401934;179401933
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-130
• Domain position: 12
• Structural Position: 13
• Q(SASA): 0.3605
• Predicted PPI site: I

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
E/D	None	None	0.02	N	0.138	0.032	0.115124310173	gnomAD-4.0.0	1.80048E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.96875E-05	0	0
E/G	None	None	0.939	N	0.565	0.417	0.42828666871	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
E/K	rs72648278	0.348	0.989	N	0.485	0.25	None	gnomAD-2.1.1	3.26605E-04	None	None	None	None	I	None	1.2408E-04	5.68E-05	None	0	0	None	0	None	2.81645E-04	5.97672E-04	4.24809E-04
E/K	rs72648278	0.348	0.989	N	0.485	0.25	None	gnomAD-3.1.2	3.81358E-04	None	None	None	None	I	None	9.65E-05	0	0	0	0	None	4.73126E-04	0	7.0553E-04	0	4.78011E-04
E/K	rs72648278	0.348	0.989	N	0.485	0.25	None	gnomAD-4.0.0	5.39021E-04	None	None	None	None	I	None	1.06918E-04	3.34079E-05	None	0	0	None	3.75799E-04	0	6.86352E-04	0	4.17135E-04

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
E/A	0.5302	ambiguous	0.4915	ambiguous	-0.517	Destabilizing	0.939	D	0.579	neutral	N	0.477557686	None	None	I
E/C	0.9829	likely_pathogenic	0.9757	pathogenic	-0.22	Destabilizing	0.999	D	0.712	prob.delet.	None	None	None	None	I
E/D	0.188	likely_benign	0.1937	benign	-0.406	Destabilizing	0.02	N	0.138	neutral	N	0.401347774	None	None	I
E/F	0.9821	likely_pathogenic	0.9741	pathogenic	-0.225	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	I
E/G	0.5379	ambiguous	0.5172	ambiguous	-0.732	Destabilizing	0.939	D	0.565	neutral	N	0.474845455	None	None	I
E/H	0.8679	likely_pathogenic	0.8245	pathogenic	0.087	Stabilizing	0.999	D	0.562	neutral	None	None	None	None	I
E/I	0.9095	likely_pathogenic	0.8748	pathogenic	0.025	Stabilizing	0.993	D	0.747	deleterious	None	None	None	None	I
E/K	0.612	likely_pathogenic	0.5459	ambiguous	0.274	Stabilizing	0.989	D	0.485	neutral	N	0.468266199	None	None	I
E/L	0.8923	likely_pathogenic	0.8488	pathogenic	0.025	Stabilizing	0.993	D	0.736	prob.delet.	None	None	None	None	I
E/M	0.9206	likely_pathogenic	0.8868	pathogenic	0.083	Stabilizing	0.999	D	0.684	prob.neutral	None	None	None	None	I
E/N	0.583	likely_pathogenic	0.5343	ambiguous	-0.236	Destabilizing	0.973	D	0.579	neutral	None	None	None	None	I
E/P	0.9724	likely_pathogenic	0.9712	pathogenic	-0.136	Destabilizing	0.993	D	0.736	prob.delet.	None	None	None	None	I
E/Q	0.4602	ambiguous	0.3944	ambiguous	-0.177	Destabilizing	0.996	D	0.565	neutral	N	0.467458123	None	None	I
E/R	0.7779	likely_pathogenic	0.7299	pathogenic	0.557	Stabilizing	0.993	D	0.623	neutral	None	None	None	None	I
E/S	0.5115	ambiguous	0.4812	ambiguous	-0.374	Destabilizing	0.953	D	0.489	neutral	None	None	None	None	I
E/T	0.603	likely_pathogenic	0.5452	ambiguous	-0.189	Destabilizing	0.993	D	0.659	neutral	None	None	None	None	I
E/V	0.7601	likely_pathogenic	0.6855	pathogenic	-0.136	Destabilizing	0.991	D	0.709	prob.delet.	N	0.475808247	None	None	I
E/W	0.9936	likely_pathogenic	0.9909	pathogenic	-0.001	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	I
E/Y	0.9528	likely_pathogenic	0.9365	pathogenic	0.033	Stabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	I

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.