TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20106	60541;60542;60543	chr2:178591409;178591408;178591407	chr2:179456136;179456135;179456134
N2AB	18465	55618;55619;55620	chr2:178591409;178591408;178591407	chr2:179456136;179456135;179456134
N2A	17538	52837;52838;52839	chr2:178591409;178591408;178591407	chr2:179456136;179456135;179456134
N2B	11041	33346;33347;33348	chr2:178591409;178591408;178591407	chr2:179456136;179456135;179456134
Novex-1	11166	33721;33722;33723	chr2:178591409;178591408;178591407	chr2:179456136;179456135;179456134
Novex-2	11233	33922;33923;33924	chr2:178591409;178591408;178591407	chr2:179456136;179456135;179456134
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-120
• Domain position: 27
• Structural Position: 42
• Q(SASA): 0.5147
• 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/T	rs1576103220	None	1.0	D	0.743	0.563	0.597732455086	gnomAD-4.0.0	6.85284E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00281E-07	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	0.9023	likely_pathogenic	0.965	pathogenic	-0.549	Destabilizing	1.0	D	0.731	prob.delet.	D	0.542693298	None	None	I
P/C	0.9924	likely_pathogenic	0.9979	pathogenic	-0.628	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	I
P/D	0.9855	likely_pathogenic	0.9946	pathogenic	-0.523	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	I
P/E	0.9815	likely_pathogenic	0.9939	pathogenic	-0.645	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
P/F	0.996	likely_pathogenic	0.999	pathogenic	-0.815	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
P/G	0.9729	likely_pathogenic	0.99	pathogenic	-0.671	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	I
P/H	0.9773	likely_pathogenic	0.993	pathogenic	-0.265	Destabilizing	1.0	D	0.773	deleterious	D	0.607367303	None	None	I
P/I	0.9755	likely_pathogenic	0.991	pathogenic	-0.38	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	I
P/K	0.9862	likely_pathogenic	0.9948	pathogenic	-0.561	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
P/L	0.9115	likely_pathogenic	0.9668	pathogenic	-0.38	Destabilizing	1.0	D	0.747	deleterious	D	0.598080717	None	None	I
P/M	0.9806	likely_pathogenic	0.9936	pathogenic	-0.401	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
P/N	0.9843	likely_pathogenic	0.9943	pathogenic	-0.278	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
P/Q	0.9743	likely_pathogenic	0.9922	pathogenic	-0.546	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
P/R	0.9667	likely_pathogenic	0.9875	pathogenic	0.001	Stabilizing	1.0	D	0.763	deleterious	D	0.639234581	None	None	I
P/S	0.9633	likely_pathogenic	0.9887	pathogenic	-0.589	Destabilizing	1.0	D	0.745	deleterious	D	0.562923921	None	None	I
P/T	0.9242	likely_pathogenic	0.9749	pathogenic	-0.617	Destabilizing	1.0	D	0.743	deleterious	D	0.601856072	None	None	I
P/V	0.9546	likely_pathogenic	0.982	pathogenic	-0.402	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
P/W	0.9978	likely_pathogenic	0.9993	pathogenic	-0.892	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
P/Y	0.9947	likely_pathogenic	0.9985	pathogenic	-0.605	Destabilizing	1.0	D	0.802	deleterious	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.