TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5023	15292;15293;15294	chr2:178734857;178734856;178734855	chr2:179599584;179599583;179599582
N2AB	4706	14341;14342;14343	chr2:178734857;178734856;178734855	chr2:179599584;179599583;179599582
N2A	3779	11560;11561;11562	chr2:178734857;178734856;178734855	chr2:179599584;179599583;179599582
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: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-33
• Domain position: 43
• Structural Position: 59
• Q(SASA): 0.6862
• 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
S/N	rs878907513	0.065	None	N	0.125	0.134	None	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
S/N	rs878907513	0.065	None	N	0.125	0.134	None	gnomAD-4.0.0	1.98436E-05	None	None	None	None	N	None	2.98793E-05	0	None	0	0	None	0	0	2.42863E-05	0	1.65673E-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
S/A	0.0712	likely_benign	0.0655	benign	-0.08	Destabilizing	0.007	N	0.16	neutral	None	None	None	None	N
S/C	0.0854	likely_benign	0.0852	benign	-0.316	Destabilizing	0.612	D	0.337	neutral	D	0.574558587	None	None	N
S/D	0.1912	likely_benign	0.1529	benign	0.14	Stabilizing	0.016	N	0.173	neutral	None	None	None	None	N
S/E	0.2402	likely_benign	0.1904	benign	0.041	Stabilizing	0.016	N	0.187	neutral	None	None	None	None	N
S/F	0.1358	likely_benign	0.1227	benign	-0.802	Destabilizing	0.214	N	0.396	neutral	None	None	None	None	N
S/G	0.0717	likely_benign	0.0714	benign	-0.143	Destabilizing	0.012	N	0.174	neutral	N	0.497861686	None	None	N
S/H	0.1322	likely_benign	0.104	benign	-0.484	Destabilizing	0.001	N	0.224	neutral	None	None	None	None	N
S/I	0.0932	likely_benign	0.0815	benign	-0.05	Destabilizing	0.029	N	0.416	neutral	N	0.513252542	None	None	N
S/K	0.2215	likely_benign	0.1596	benign	-0.317	Destabilizing	0.001	N	0.181	neutral	None	None	None	None	N
S/L	0.0779	likely_benign	0.0737	benign	-0.05	Destabilizing	None	N	0.241	neutral	None	None	None	None	N
S/M	0.1343	likely_benign	0.1206	benign	-0.113	Destabilizing	0.214	N	0.342	neutral	None	None	None	None	N
S/N	0.0707	likely_benign	0.0653	benign	-0.059	Destabilizing	None	N	0.125	neutral	N	0.496170762	None	None	N
S/P	0.13	likely_benign	0.1042	benign	-0.034	Destabilizing	0.136	N	0.382	neutral	None	None	None	None	N
S/Q	0.1986	likely_benign	0.1528	benign	-0.26	Destabilizing	0.001	N	0.165	neutral	None	None	None	None	N
S/R	0.1774	likely_benign	0.1284	benign	-0.094	Destabilizing	None	N	0.257	neutral	N	0.469923524	None	None	N
S/T	0.0606	likely_benign	0.0578	benign	-0.154	Destabilizing	None	N	0.17	neutral	N	0.45064483	None	None	N
S/V	0.1123	likely_benign	0.094	benign	-0.034	Destabilizing	0.038	N	0.363	neutral	None	None	None	None	N
S/W	0.2004	likely_benign	0.1928	benign	-0.907	Destabilizing	0.864	D	0.377	neutral	None	None	None	None	N
S/Y	0.1142	likely_benign	0.1016	benign	-0.57	Destabilizing	0.214	N	0.407	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.