TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32262	97009;97010;97011	chr2:178543189;178543188;178543187	chr2:179407916;179407915;179407914
N2AB	30621	92086;92087;92088	chr2:178543189;178543188;178543187	chr2:179407916;179407915;179407914
N2A	29694	89305;89306;89307	chr2:178543189;178543188;178543187	chr2:179407916;179407915;179407914
N2B	23197	69814;69815;69816	chr2:178543189;178543188;178543187	chr2:179407916;179407915;179407914
Novex-1	23322	70189;70190;70191	chr2:178543189;178543188;178543187	chr2:179407916;179407915;179407914
Novex-2	23389	70390;70391;70392	chr2:178543189;178543188;178543187	chr2:179407916;179407915;179407914
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Fn3-123
• Domain position: 61
• Structural Position: 91
• Q(SASA): 0.139
• 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
H/N	rs1376767409	-2.122	0.961	N	0.466	0.318	0.297718772494	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
H/N	rs1376767409	-2.122	0.961	N	0.466	0.318	0.297718772494	gnomAD-4.0.0	2.05265E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69843E-06	0	0
H/Y	None	None	0.012	N	0.243	0.273	0.180583059064	gnomAD-4.0.0	6.84217E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65656E-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
H/A	0.4754	ambiguous	0.4583	ambiguous	-1.835	Destabilizing	0.842	D	0.546	neutral	None	None	None	None	N
H/C	0.2184	likely_benign	0.2091	benign	-1.156	Destabilizing	0.998	D	0.761	deleterious	None	None	None	None	N
H/D	0.6218	likely_pathogenic	0.6005	pathogenic	-1.892	Destabilizing	0.989	D	0.539	neutral	N	0.513574414	None	None	N
H/E	0.61	likely_pathogenic	0.6027	pathogenic	-1.697	Destabilizing	0.915	D	0.457	neutral	None	None	None	None	N
H/F	0.3253	likely_benign	0.3262	benign	-0.04	Destabilizing	0.016	N	0.403	neutral	None	None	None	None	N
H/G	0.5264	ambiguous	0.5004	ambiguous	-2.265	Highly Destabilizing	0.915	D	0.538	neutral	None	None	None	None	N
H/I	0.5882	likely_pathogenic	0.5727	pathogenic	-0.561	Destabilizing	0.949	D	0.641	neutral	None	None	None	None	N
H/K	0.5241	ambiguous	0.5334	ambiguous	-1.247	Destabilizing	0.974	D	0.532	neutral	None	None	None	None	N
H/L	0.2864	likely_benign	0.2721	benign	-0.561	Destabilizing	0.669	D	0.607	neutral	N	0.404673294	None	None	N
H/M	0.6279	likely_pathogenic	0.6255	pathogenic	-0.811	Destabilizing	0.998	D	0.672	neutral	None	None	None	None	N
H/N	0.2251	likely_benign	0.2156	benign	-2.057	Highly Destabilizing	0.961	D	0.466	neutral	N	0.513574414	None	None	N
H/P	0.8693	likely_pathogenic	0.8798	pathogenic	-0.976	Destabilizing	0.989	D	0.649	neutral	N	0.47038128	None	None	N
H/Q	0.3595	ambiguous	0.3467	ambiguous	-1.703	Destabilizing	0.989	D	0.47	neutral	N	0.494988654	None	None	N
H/R	0.3043	likely_benign	0.2988	benign	-1.505	Destabilizing	0.966	D	0.463	neutral	N	0.47012779	None	None	N
H/S	0.4286	ambiguous	0.4176	ambiguous	-2.159	Highly Destabilizing	0.915	D	0.495	neutral	None	None	None	None	N
H/T	0.4696	ambiguous	0.4731	ambiguous	-1.825	Destabilizing	0.974	D	0.569	neutral	None	None	None	None	N
H/V	0.4632	ambiguous	0.4561	ambiguous	-0.976	Destabilizing	0.842	D	0.631	neutral	None	None	None	None	N
H/W	0.5423	ambiguous	0.5572	ambiguous	0.627	Stabilizing	0.993	D	0.671	neutral	None	None	None	None	N
H/Y	0.0855	likely_benign	0.088	benign	0.377	Stabilizing	0.012	N	0.243	neutral	N	0.361554448	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.