TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19816	59671;59672;59673	chr2:178592559;178592558;178592557	chr2:179457286;179457285;179457284
N2AB	18175	54748;54749;54750	chr2:178592559;178592558;178592557	chr2:179457286;179457285;179457284
N2A	17248	51967;51968;51969	chr2:178592559;178592558;178592557	chr2:179457286;179457285;179457284
N2B	10751	32476;32477;32478	chr2:178592559;178592558;178592557	chr2:179457286;179457285;179457284
Novex-1	10876	32851;32852;32853	chr2:178592559;178592558;178592557	chr2:179457286;179457285;179457284
Novex-2	10943	33052;33053;33054	chr2:178592559;178592558;178592557	chr2:179457286;179457285;179457284
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-119
• Domain position: 27
• Structural Position: 44
• Q(SASA): 0.0951
• 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
P/L	rs2050451643	None	1.0	D	0.827	0.63	0.694042930181	gnomAD-4.0.0	1.59184E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85948E-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	0.9485	likely_pathogenic	0.9471	pathogenic	-1.581	Destabilizing	1.0	D	0.783	deleterious	D	0.522383317	None	None	N
P/C	0.9935	likely_pathogenic	0.9929	pathogenic	-1.053	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
P/D	0.9998	likely_pathogenic	0.9998	pathogenic	-1.517	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
P/E	0.999	likely_pathogenic	0.9992	pathogenic	-1.401	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
P/F	0.9997	likely_pathogenic	0.9997	pathogenic	-1.038	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
P/G	0.9946	likely_pathogenic	0.9948	pathogenic	-2.02	Highly Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
P/H	0.9984	likely_pathogenic	0.9987	pathogenic	-1.738	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
P/I	0.9963	likely_pathogenic	0.9971	pathogenic	-0.425	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
P/K	0.9993	likely_pathogenic	0.9995	pathogenic	-1.26	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
P/L	0.9791	likely_pathogenic	0.9816	pathogenic	-0.425	Destabilizing	1.0	D	0.827	deleterious	D	0.533482451	None	None	N
P/M	0.9984	likely_pathogenic	0.9987	pathogenic	-0.366	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
P/N	0.9997	likely_pathogenic	0.9997	pathogenic	-1.282	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
P/Q	0.9971	likely_pathogenic	0.9975	pathogenic	-1.26	Destabilizing	1.0	D	0.845	deleterious	D	0.55861828	None	None	N
P/R	0.996	likely_pathogenic	0.9968	pathogenic	-0.998	Destabilizing	1.0	D	0.839	deleterious	D	0.569974585	None	None	N
P/S	0.994	likely_pathogenic	0.9941	pathogenic	-1.896	Destabilizing	1.0	D	0.824	deleterious	D	0.540007046	None	None	N
P/T	0.9937	likely_pathogenic	0.9946	pathogenic	-1.648	Destabilizing	1.0	D	0.833	deleterious	D	0.551363351	None	None	N
P/V	0.9898	likely_pathogenic	0.9915	pathogenic	-0.777	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
P/W	0.9998	likely_pathogenic	0.9998	pathogenic	-1.427	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
P/Y	0.9997	likely_pathogenic	0.9998	pathogenic	-1.03	Destabilizing	1.0	D	0.819	deleterious	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.