TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3078	9457;9458;9459	chr2:178768087;178768086;178768085	chr2:179632814;179632813;179632812
N2AB	3078	9457;9458;9459	chr2:178768087;178768086;178768085	chr2:179632814;179632813;179632812
N2A	3078	9457;9458;9459	chr2:178768087;178768086;178768085	chr2:179632814;179632813;179632812
N2B	3032	9319;9320;9321	chr2:178768087;178768086;178768085	chr2:179632814;179632813;179632812
Novex-1	3032	9319;9320;9321	chr2:178768087;178768086;178768085	chr2:179632814;179632813;179632812
Novex-2	3032	9319;9320;9321	chr2:178768087;178768086;178768085	chr2:179632814;179632813;179632812
Novex-3	3078	9457;9458;9459	chr2:178768087;178768086;178768085	chr2:179632814;179632813;179632812

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-21
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.2971
• 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/G	rs370704384	-1.05	0.822	D	0.606	0.607	None	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	6.15E-05	0	None	0	0	None	0	None	0	0	0
E/Q	rs1309287997	None	0.971	D	0.631	0.39	0.426670027402	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/Q	rs1309287997	None	0.971	D	0.631	0.39	0.426670027402	gnomAD-4.0.0	2.56117E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.7835E-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
E/A	0.7265	likely_pathogenic	0.7373	pathogenic	-0.864	Destabilizing	0.698	D	0.574	neutral	D	0.645731944	None	None	N
E/C	0.9912	likely_pathogenic	0.9922	pathogenic	-0.637	Destabilizing	0.998	D	0.715	prob.delet.	None	None	None	None	N
E/D	0.7816	likely_pathogenic	0.8093	pathogenic	-1.416	Destabilizing	0.014	N	0.309	neutral	D	0.561392695	None	None	N
E/F	0.9862	likely_pathogenic	0.988	pathogenic	-0.343	Destabilizing	0.993	D	0.756	deleterious	None	None	None	None	N
E/G	0.9061	likely_pathogenic	0.9133	pathogenic	-1.249	Destabilizing	0.822	D	0.606	neutral	D	0.667401215	None	None	N
E/H	0.9693	likely_pathogenic	0.9741	pathogenic	-0.757	Destabilizing	0.998	D	0.633	neutral	None	None	None	None	N
E/I	0.8844	likely_pathogenic	0.891	pathogenic	0.193	Stabilizing	0.978	D	0.764	deleterious	None	None	None	None	N
E/K	0.9299	likely_pathogenic	0.9317	pathogenic	-1.093	Destabilizing	0.822	D	0.538	neutral	D	0.547251361	None	None	N
E/L	0.9483	likely_pathogenic	0.95	pathogenic	0.193	Stabilizing	0.978	D	0.723	prob.delet.	None	None	None	None	N
E/M	0.9369	likely_pathogenic	0.9436	pathogenic	0.664	Stabilizing	0.998	D	0.715	prob.delet.	None	None	None	None	N
E/N	0.946	likely_pathogenic	0.9541	pathogenic	-1.443	Destabilizing	0.754	D	0.576	neutral	None	None	None	None	N
E/P	0.9986	likely_pathogenic	0.9983	pathogenic	-0.138	Destabilizing	0.978	D	0.717	prob.delet.	None	None	None	None	N
E/Q	0.6444	likely_pathogenic	0.6679	pathogenic	-1.285	Destabilizing	0.971	D	0.631	neutral	D	0.574181807	None	None	N
E/R	0.9519	likely_pathogenic	0.9497	pathogenic	-0.807	Destabilizing	0.978	D	0.632	neutral	None	None	None	None	N
E/S	0.7404	likely_pathogenic	0.7611	pathogenic	-1.803	Destabilizing	0.193	N	0.407	neutral	None	None	None	None	N
E/T	0.7421	likely_pathogenic	0.7708	pathogenic	-1.494	Destabilizing	0.754	D	0.621	neutral	None	None	None	None	N
E/V	0.7464	likely_pathogenic	0.7558	pathogenic	-0.138	Destabilizing	0.971	D	0.701	prob.neutral	D	0.587684786	None	None	N
E/W	0.9969	likely_pathogenic	0.9973	pathogenic	-0.192	Destabilizing	0.998	D	0.68	prob.neutral	None	None	None	None	N
E/Y	0.9834	likely_pathogenic	0.9856	pathogenic	-0.143	Destabilizing	0.993	D	0.735	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.