TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23522	70789;70790;70791	chr2:178575568;178575567;178575566	chr2:179440295;179440294;179440293
N2AB	21881	65866;65867;65868	chr2:178575568;178575567;178575566	chr2:179440295;179440294;179440293
N2A	20954	63085;63086;63087	chr2:178575568;178575567;178575566	chr2:179440295;179440294;179440293
N2B	14457	43594;43595;43596	chr2:178575568;178575567;178575566	chr2:179440295;179440294;179440293
Novex-1	14582	43969;43970;43971	chr2:178575568;178575567;178575566	chr2:179440295;179440294;179440293
Novex-2	14649	44170;44171;44172	chr2:178575568;178575567;178575566	chr2:179440295;179440294;179440293
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: Fn3-58
• Domain position: 88
• Structural Position: 122
• Q(SASA): 0.3561
• 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
E/K	rs561586925	-0.34	0.995	N	0.805	0.302	0.476908202251	gnomAD-2.1.1	2.41E-05	None	None	None	None	N	None	0	8.69E-05	None	0	0	None	0	None	0	8.9E-06	3.31895E-04
E/K	rs561586925	-0.34	0.995	N	0.805	0.302	0.476908202251	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	1.96515E-04	0	0	0	None	0	0	0	0	0
E/K	rs561586925	-0.34	0.995	N	0.805	0.302	0.476908202251	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
E/K	rs561586925	-0.34	0.995	N	0.805	0.302	0.476908202251	gnomAD-4.0.0	7.43646E-06	None	None	None	None	N	None	0	8.33222E-05	None	0	0	None	0	0	4.2385E-06	0	3.20123E-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
E/A	0.2967	likely_benign	0.377	ambiguous	-0.86	Destabilizing	0.99	D	0.785	deleterious	N	0.514206346	None	None	N
E/C	0.921	likely_pathogenic	0.9452	pathogenic	-0.401	Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
E/D	0.2688	likely_benign	0.3079	benign	-0.941	Destabilizing	0.928	D	0.747	deleterious	N	0.470124109	None	None	N
E/F	0.8918	likely_pathogenic	0.9213	pathogenic	0.043	Stabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
E/G	0.4979	ambiguous	0.5982	pathogenic	-1.266	Destabilizing	0.999	D	0.721	deleterious	N	0.483179162	None	None	N
E/H	0.7828	likely_pathogenic	0.8359	pathogenic	-0.092	Destabilizing	1.0	D	0.737	deleterious	None	None	None	None	N
E/I	0.486	ambiguous	0.5995	pathogenic	0.268	Stabilizing	0.998	D	0.823	deleterious	None	None	None	None	N
E/K	0.4349	ambiguous	0.5498	ambiguous	-0.385	Destabilizing	0.995	D	0.805	deleterious	N	0.474265166	None	None	N
E/L	0.6229	likely_pathogenic	0.7205	pathogenic	0.268	Stabilizing	0.998	D	0.727	deleterious	None	None	None	None	N
E/M	0.5939	likely_pathogenic	0.6929	pathogenic	0.707	Stabilizing	0.996	D	0.837	deleterious	None	None	None	None	N
E/N	0.5788	likely_pathogenic	0.679	pathogenic	-1.082	Destabilizing	0.995	D	0.759	deleterious	None	None	None	None	N
E/P	0.8849	likely_pathogenic	0.9179	pathogenic	-0.087	Destabilizing	0.984	D	0.741	deleterious	None	None	None	None	N
E/Q	0.2866	likely_benign	0.3505	ambiguous	-0.903	Destabilizing	0.998	D	0.767	deleterious	N	0.472138799	None	None	N
E/R	0.6337	likely_pathogenic	0.7369	pathogenic	-0.036	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
E/S	0.4027	ambiguous	0.5049	ambiguous	-1.429	Destabilizing	0.992	D	0.787	deleterious	None	None	None	None	N
E/T	0.3623	ambiguous	0.4845	ambiguous	-1.07	Destabilizing	0.998	D	0.715	prob.delet.	None	None	None	None	N
E/V	0.2809	likely_benign	0.3745	ambiguous	-0.087	Destabilizing	0.995	D	0.753	deleterious	N	0.483495104	None	None	N
E/W	0.9757	likely_pathogenic	0.9834	pathogenic	0.426	Stabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/Y	0.8585	likely_pathogenic	0.8969	pathogenic	0.358	Stabilizing	1.0	D	0.848	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.