TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9232	27919;27920;27921	chr2:178712136;178712135;178712134	chr2:179576863;179576862;179576861
N2AB	8915	26968;26969;26970	chr2:178712136;178712135;178712134	chr2:179576863;179576862;179576861
N2A	7988	24187;24188;24189	chr2:178712136;178712135;178712134	chr2:179576863;179576862;179576861
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: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-78
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.695
• Predicted PPI site: I

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
P/L	rs1354298331	0.039	0.942	D	0.529	0.702	0.839298628363	gnomAD-2.1.1	8.05E-06	None	None	None	None	I	None	6.52E-05	2.9E-05	None	0	0	None	0	None	0	0	0
P/L	rs1354298331	0.039	0.942	D	0.529	0.702	0.839298628363	gnomAD-4.0.0	1.59123E-06	None	None	None	None	I	None	0	2.28686E-05	None	0	0	None	0	0	0	0	0
P/S	rs1228009511	0.077	0.942	D	0.407	0.725	0.585777056924	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
P/S	rs1228009511	0.077	0.942	D	0.407	0.725	0.585777056924	gnomAD-4.0.0	1.59122E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85817E-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
P/A	0.7195	likely_pathogenic	0.9467	pathogenic	-0.618	Destabilizing	0.822	D	0.448	neutral	D	0.553555851	None	None	I
P/C	0.9836	likely_pathogenic	0.9977	pathogenic	-0.628	Destabilizing	0.998	D	0.61	neutral	None	None	None	None	I
P/D	0.9655	likely_pathogenic	0.9922	pathogenic	-0.439	Destabilizing	0.956	D	0.411	neutral	None	None	None	None	I
P/E	0.9085	likely_pathogenic	0.9854	pathogenic	-0.559	Destabilizing	0.86	D	0.424	neutral	None	None	None	None	I
P/F	0.9894	likely_pathogenic	0.9987	pathogenic	-0.843	Destabilizing	0.988	D	0.558	neutral	None	None	None	None	I
P/G	0.92	likely_pathogenic	0.9749	pathogenic	-0.753	Destabilizing	0.956	D	0.418	neutral	None	None	None	None	I
P/H	0.9345	likely_pathogenic	0.9905	pathogenic	-0.344	Destabilizing	0.071	N	0.334	neutral	D	0.625708311	None	None	I
P/I	0.9567	likely_pathogenic	0.992	pathogenic	-0.409	Destabilizing	0.978	D	0.572	neutral	None	None	None	None	I
P/K	0.9386	likely_pathogenic	0.9902	pathogenic	-0.557	Destabilizing	0.754	D	0.469	neutral	None	None	None	None	I
P/L	0.8282	likely_pathogenic	0.9675	pathogenic	-0.409	Destabilizing	0.942	D	0.529	neutral	D	0.60272401	None	None	I
P/M	0.9467	likely_pathogenic	0.992	pathogenic	-0.368	Destabilizing	0.998	D	0.444	neutral	None	None	None	None	I
P/N	0.9598	likely_pathogenic	0.9911	pathogenic	-0.258	Destabilizing	0.915	D	0.465	neutral	None	None	None	None	I
P/Q	0.8824	likely_pathogenic	0.983	pathogenic	-0.532	Destabilizing	0.956	D	0.403	neutral	None	None	None	None	I
P/R	0.8717	likely_pathogenic	0.9795	pathogenic	-0.001	Destabilizing	0.032	N	0.337	neutral	D	0.618571927	None	None	I
P/S	0.8647	likely_pathogenic	0.9742	pathogenic	-0.61	Destabilizing	0.942	D	0.407	neutral	D	0.556011387	None	None	I
P/T	0.7771	likely_pathogenic	0.9441	pathogenic	-0.633	Destabilizing	0.971	D	0.399	neutral	D	0.618571927	None	None	I
P/V	0.9003	likely_pathogenic	0.9781	pathogenic	-0.444	Destabilizing	0.978	D	0.467	neutral	None	None	None	None	I
P/W	0.9906	likely_pathogenic	0.9992	pathogenic	-0.911	Destabilizing	0.998	D	0.617	neutral	None	None	None	None	I
P/Y	0.984	likely_pathogenic	0.998	pathogenic	-0.622	Destabilizing	0.915	D	0.571	neutral	None	None	None	None	I

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.