TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30135	90628;90629;90630	chr2:178552497;178552496;178552495	chr2:179417224;179417223;179417222
N2AB	28494	85705;85706;85707	chr2:178552497;178552496;178552495	chr2:179417224;179417223;179417222
N2A	27567	82924;82925;82926	chr2:178552497;178552496;178552495	chr2:179417224;179417223;179417222
N2B	21070	63433;63434;63435	chr2:178552497;178552496;178552495	chr2:179417224;179417223;179417222
Novex-1	21195	63808;63809;63810	chr2:178552497;178552496;178552495	chr2:179417224;179417223;179417222
Novex-2	21262	64009;64010;64011	chr2:178552497;178552496;178552495	chr2:179417224;179417223;179417222
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-148
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.7502
• 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
D/A	None	None	0.124	N	0.516	0.157	0.329282125956	gnomAD-4.0.0	1.36906E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79979E-06	0	0
D/Y	rs1345842095	None	0.859	N	0.615	0.286	0.626665467207	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
D/Y	rs1345842095	None	0.859	N	0.615	0.286	0.626665467207	gnomAD-4.0.0	2.47984E-06	None	None	None	None	N	None	1.33486E-05	0	None	0	0	None	0	0	2.54395E-06	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
D/A	0.1147	likely_benign	0.0977	benign	0.036	Stabilizing	0.124	N	0.516	neutral	N	0.519298026	None	None	N
D/C	0.4477	ambiguous	0.388	ambiguous	0.005	Stabilizing	0.968	D	0.679	prob.neutral	None	None	None	None	N
D/E	0.1006	likely_benign	0.0874	benign	-0.239	Destabilizing	None	N	0.211	neutral	N	0.420613899	None	None	N
D/F	0.4883	ambiguous	0.4102	ambiguous	-0.017	Destabilizing	0.89	D	0.617	neutral	None	None	None	None	N
D/G	0.1064	likely_benign	0.0944	benign	-0.104	Destabilizing	0.001	N	0.273	neutral	N	0.482473221	None	None	N
D/H	0.2219	likely_benign	0.1806	benign	0.448	Stabilizing	0.883	D	0.544	neutral	N	0.501579057	None	None	N
D/I	0.2642	likely_benign	0.2095	benign	0.338	Stabilizing	0.726	D	0.606	neutral	None	None	None	None	N
D/K	0.2425	likely_benign	0.1998	benign	0.508	Stabilizing	0.157	N	0.507	neutral	None	None	None	None	N
D/L	0.2663	likely_benign	0.2198	benign	0.338	Stabilizing	0.567	D	0.597	neutral	None	None	None	None	N
D/M	0.4455	ambiguous	0.3864	ambiguous	0.209	Stabilizing	0.968	D	0.635	neutral	None	None	None	None	N
D/N	0.0883	likely_benign	0.081	benign	0.24	Stabilizing	0.22	N	0.515	neutral	N	0.519124668	None	None	N
D/P	0.5181	ambiguous	0.4616	ambiguous	0.258	Stabilizing	0.726	D	0.532	neutral	None	None	None	None	N
D/Q	0.2176	likely_benign	0.1867	benign	0.261	Stabilizing	0.396	N	0.483	neutral	None	None	None	None	N
D/R	0.308	likely_benign	0.2539	benign	0.701	Stabilizing	0.396	N	0.586	neutral	None	None	None	None	N
D/S	0.0959	likely_benign	0.0879	benign	0.156	Stabilizing	0.157	N	0.499	neutral	None	None	None	None	N
D/T	0.1641	likely_benign	0.1433	benign	0.271	Stabilizing	0.272	N	0.495	neutral	None	None	None	None	N
D/V	0.1637	likely_benign	0.1321	benign	0.258	Stabilizing	0.497	N	0.573	neutral	N	0.520164818	None	None	N
D/W	0.8091	likely_pathogenic	0.7588	pathogenic	0.034	Stabilizing	0.968	D	0.68	prob.neutral	None	None	None	None	N
D/Y	0.2175	likely_benign	0.1735	benign	0.213	Stabilizing	0.859	D	0.615	neutral	N	0.501925774	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.