TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3192	9799;9800;9801	chr2:178766510;178766509;178766508	chr2:179631237;179631236;179631235
N2AB	3192	9799;9800;9801	chr2:178766510;178766509;178766508	chr2:179631237;179631236;179631235
N2A	3192	9799;9800;9801	chr2:178766510;178766509;178766508	chr2:179631237;179631236;179631235
N2B	3146	9661;9662;9663	chr2:178766510;178766509;178766508	chr2:179631237;179631236;179631235
Novex-1	3146	9661;9662;9663	chr2:178766510;178766509;178766508	chr2:179631237;179631236;179631235
Novex-2	3146	9661;9662;9663	chr2:178766510;178766509;178766508	chr2:179631237;179631236;179631235
Novex-3	3192	9799;9800;9801	chr2:178766510;178766509;178766508	chr2:179631237;179631236;179631235

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-22
• Domain position: 46
• Structural Position: 111
• Q(SASA): 0.6324
• 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	rs868040631	None	0.984	N	0.489	0.201	0.212008924253	gnomAD-4.0.0	1.59056E-06	None	None	None	None	N	None	5.65163E-05	0	None	0	0	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
E/A	0.2615	likely_benign	0.3649	ambiguous	-0.019	Destabilizing	0.992	D	0.518	neutral	N	0.344268074	None	None	N
E/C	0.9618	likely_pathogenic	0.9779	pathogenic	-0.104	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
E/D	0.1532	likely_benign	0.1426	benign	-0.255	Destabilizing	0.992	D	0.413	neutral	N	0.345717755	None	None	N
E/F	0.9282	likely_pathogenic	0.9699	pathogenic	-0.061	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
E/G	0.185	likely_benign	0.2813	benign	-0.14	Destabilizing	0.999	D	0.521	neutral	N	0.332793272	None	None	N
E/H	0.7107	likely_pathogenic	0.8181	pathogenic	0.479	Stabilizing	1.0	D	0.669	neutral	None	None	None	None	N
E/I	0.7305	likely_pathogenic	0.8444	pathogenic	0.241	Stabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
E/K	0.2546	likely_benign	0.4446	ambiguous	0.464	Stabilizing	0.984	D	0.489	neutral	N	0.341394226	None	None	N
E/L	0.6938	likely_pathogenic	0.8089	pathogenic	0.241	Stabilizing	0.998	D	0.655	neutral	None	None	None	None	N
E/M	0.7421	likely_pathogenic	0.8501	pathogenic	0.063	Stabilizing	1.0	D	0.625	neutral	None	None	None	None	N
E/N	0.3797	ambiguous	0.4686	ambiguous	0.231	Stabilizing	0.999	D	0.641	neutral	None	None	None	None	N
E/P	0.5582	ambiguous	0.6191	pathogenic	0.172	Stabilizing	1.0	D	0.589	neutral	None	None	None	None	N
E/Q	0.2416	likely_benign	0.3459	ambiguous	0.244	Stabilizing	0.916	D	0.297	neutral	N	0.351132362	None	None	N
E/R	0.4512	ambiguous	0.6561	pathogenic	0.662	Stabilizing	0.998	D	0.643	neutral	None	None	None	None	N
E/S	0.3096	likely_benign	0.3943	ambiguous	0.091	Stabilizing	0.994	D	0.545	neutral	None	None	None	None	N
E/T	0.4423	ambiguous	0.5579	ambiguous	0.197	Stabilizing	0.999	D	0.577	neutral	None	None	None	None	N
E/V	0.4938	ambiguous	0.6449	pathogenic	0.172	Stabilizing	0.999	D	0.598	neutral	N	0.364675245	None	None	N
E/W	0.9575	likely_pathogenic	0.9823	pathogenic	-0.015	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
E/Y	0.8397	likely_pathogenic	0.9178	pathogenic	0.164	Stabilizing	1.0	D	0.635	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.