TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4946	15061;15062;15063	chr2:178735610;178735609;178735608	chr2:179600337;179600336;179600335
N2AB	4629	14110;14111;14112	chr2:178735610;178735609;178735608	chr2:179600337;179600336;179600335
N2A	3702	11329;11330;11331	chr2:178735610;178735609;178735608	chr2:179600337;179600336;179600335
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-32
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.2311
• 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/D	rs1169291552	None	0.054	D	0.233	0.231	0.328486982098	gnomAD-4.0.0	4.77567E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.57638E-06	0	0
E/K	rs2081307227	None	0.978	N	0.503	0.377	0.366277470483	gnomAD-4.0.0	2.053E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99525E-07	0	3.31455E-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	0.2079	likely_benign	0.2021	benign	-0.864	Destabilizing	0.989	D	0.553	neutral	N	0.509215723	None	None	N
E/C	0.8433	likely_pathogenic	0.8243	pathogenic	-0.683	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
E/D	0.1854	likely_benign	0.1853	benign	-1.549	Destabilizing	0.054	N	0.233	neutral	D	0.567560849	None	None	N
E/F	0.7215	likely_pathogenic	0.7067	pathogenic	-0.452	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
E/G	0.2915	likely_benign	0.2823	benign	-1.265	Destabilizing	0.978	D	0.626	neutral	D	0.601225419	None	None	N
E/H	0.4318	ambiguous	0.4302	ambiguous	-0.901	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
E/I	0.2952	likely_benign	0.2723	benign	0.247	Stabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
E/K	0.2499	likely_benign	0.2329	benign	-1.239	Destabilizing	0.978	D	0.503	neutral	N	0.500449263	None	None	N
E/L	0.409	ambiguous	0.3941	ambiguous	0.247	Stabilizing	0.998	D	0.747	deleterious	None	None	None	None	N
E/M	0.438	ambiguous	0.4157	ambiguous	0.774	Stabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
E/N	0.3256	likely_benign	0.3223	benign	-1.588	Destabilizing	0.995	D	0.617	neutral	None	None	None	None	N
E/P	0.974	likely_pathogenic	0.9716	pathogenic	-0.102	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
E/Q	0.1343	likely_benign	0.1333	benign	-1.38	Destabilizing	0.997	D	0.616	neutral	N	0.508607118	None	None	N
E/R	0.3463	ambiguous	0.3363	benign	-1.038	Destabilizing	0.998	D	0.67	neutral	None	None	None	None	N
E/S	0.2362	likely_benign	0.2308	benign	-1.997	Destabilizing	0.983	D	0.501	neutral	None	None	None	None	N
E/T	0.226	likely_benign	0.2188	benign	-1.664	Destabilizing	0.998	D	0.692	prob.neutral	None	None	None	None	N
E/V	0.1836	likely_benign	0.1705	benign	-0.102	Destabilizing	0.999	D	0.727	prob.delet.	N	0.498490791	None	None	N
E/W	0.8551	likely_pathogenic	0.8402	pathogenic	-0.406	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
E/Y	0.5941	likely_pathogenic	0.5737	pathogenic	-0.274	Destabilizing	1.0	D	0.739	prob.delet.	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.