TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2563	7912;7913;7914	chr2:178773277;178773276;178773275	chr2:179638004;179638003;179638002
N2AB	2563	7912;7913;7914	chr2:178773277;178773276;178773275	chr2:179638004;179638003;179638002
N2A	2563	7912;7913;7914	chr2:178773277;178773276;178773275	chr2:179638004;179638003;179638002
N2B	2517	7774;7775;7776	chr2:178773277;178773276;178773275	chr2:179638004;179638003;179638002
Novex-1	2517	7774;7775;7776	chr2:178773277;178773276;178773275	chr2:179638004;179638003;179638002
Novex-2	2517	7774;7775;7776	chr2:178773277;178773276;178773275	chr2:179638004;179638003;179638002
Novex-3	2563	7912;7913;7914	chr2:178773277;178773276;178773275	chr2:179638004;179638003;179638002

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-15
• Domain position: 31
• Structural Position: 46
• Q(SASA): 0.1565
• 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
V/D	rs775758080	-2.187	0.959	D	0.766	0.908	0.879622353233	gnomAD-2.1.1	7.98E-06	None	None	None	None	N	None	0	5.8E-05	None	0	0	None	0	None	0	0	0
V/D	rs775758080	-2.187	0.959	D	0.766	0.908	0.879622353233	gnomAD-4.0.0	3.18177E-06	None	None	None	None	N	None	0	4.5754E-05	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
V/A	0.2653	likely_benign	0.2469	benign	-1.723	Destabilizing	0.061	N	0.328	neutral	D	0.540200853	None	None	N
V/C	0.8023	likely_pathogenic	0.7965	pathogenic	-1.179	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
V/D	0.8908	likely_pathogenic	0.8712	pathogenic	-2.018	Highly Destabilizing	0.959	D	0.766	deleterious	D	0.674978346	None	None	N
V/E	0.8353	likely_pathogenic	0.81	pathogenic	-1.825	Destabilizing	0.969	D	0.737	prob.delet.	None	None	None	None	N
V/F	0.5239	ambiguous	0.474	ambiguous	-1.149	Destabilizing	0.996	D	0.707	prob.neutral	D	0.653163753	None	None	N
V/G	0.4425	ambiguous	0.4157	ambiguous	-2.151	Highly Destabilizing	0.852	D	0.718	prob.delet.	D	0.571438878	None	None	N
V/H	0.9401	likely_pathogenic	0.929	pathogenic	-1.568	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
V/I	0.1141	likely_benign	0.1092	benign	-0.541	Destabilizing	0.826	D	0.576	neutral	D	0.529367057	None	None	N
V/K	0.8656	likely_pathogenic	0.8393	pathogenic	-1.299	Destabilizing	0.939	D	0.737	prob.delet.	None	None	None	None	N
V/L	0.5727	likely_pathogenic	0.5365	ambiguous	-0.541	Destabilizing	0.826	D	0.576	neutral	D	0.654153711	None	None	N
V/M	0.4028	ambiguous	0.3686	ambiguous	-0.63	Destabilizing	0.997	D	0.586	neutral	None	None	None	None	N
V/N	0.7712	likely_pathogenic	0.7341	pathogenic	-1.619	Destabilizing	0.991	D	0.778	deleterious	None	None	None	None	N
V/P	0.6876	likely_pathogenic	0.6795	pathogenic	-0.911	Destabilizing	0.02	N	0.481	neutral	None	None	None	None	N
V/Q	0.8525	likely_pathogenic	0.8302	pathogenic	-1.497	Destabilizing	0.997	D	0.789	deleterious	None	None	None	None	N
V/R	0.833	likely_pathogenic	0.807	pathogenic	-1.175	Destabilizing	0.991	D	0.792	deleterious	None	None	None	None	N
V/S	0.5023	ambiguous	0.4635	ambiguous	-2.167	Highly Destabilizing	0.884	D	0.694	prob.neutral	None	None	None	None	N
V/T	0.3652	ambiguous	0.3411	ambiguous	-1.83	Destabilizing	0.17	N	0.351	neutral	None	None	None	None	N
V/W	0.9797	likely_pathogenic	0.9755	pathogenic	-1.437	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
V/Y	0.893	likely_pathogenic	0.8701	pathogenic	-1.066	Destabilizing	0.997	D	0.702	prob.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.