TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26501	79726;79727;79728	chr2:178566631;178566630;178566629	chr2:179431358;179431357;179431356
N2AB	24860	74803;74804;74805	chr2:178566631;178566630;178566629	chr2:179431358;179431357;179431356
N2A	23933	72022;72023;72024	chr2:178566631;178566630;178566629	chr2:179431358;179431357;179431356
N2B	17436	52531;52532;52533	chr2:178566631;178566630;178566629	chr2:179431358;179431357;179431356
Novex-1	17561	52906;52907;52908	chr2:178566631;178566630;178566629	chr2:179431358;179431357;179431356
Novex-2	17628	53107;53108;53109	chr2:178566631;178566630;178566629	chr2:179431358;179431357;179431356
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-81
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.3766
• 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
K/E	rs1310766903	None	0.41	N	0.473	0.25	0.288352970974	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/E	rs1310766903	None	0.41	N	0.473	0.25	0.288352970974	gnomAD-4.0.0	6.57505E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.4708E-05	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
K/A	0.4584	ambiguous	0.4089	ambiguous	-0.181	Destabilizing	0.648	D	0.546	neutral	None	None	None	None	N
K/C	0.668	likely_pathogenic	0.6584	pathogenic	-0.208	Destabilizing	0.993	D	0.79	deleterious	None	None	None	None	N
K/D	0.8142	likely_pathogenic	0.7691	pathogenic	-0.213	Destabilizing	0.866	D	0.727	prob.delet.	None	None	None	None	N
K/E	0.3482	ambiguous	0.3071	benign	-0.205	Destabilizing	0.41	N	0.473	neutral	N	0.515726498	None	None	N
K/F	0.9126	likely_pathogenic	0.891	pathogenic	-0.457	Destabilizing	0.98	D	0.779	deleterious	None	None	None	None	N
K/G	0.5033	ambiguous	0.4723	ambiguous	-0.415	Destabilizing	0.866	D	0.679	prob.neutral	None	None	None	None	N
K/H	0.4159	ambiguous	0.3811	ambiguous	-0.892	Destabilizing	0.98	D	0.697	prob.neutral	None	None	None	None	N
K/I	0.6309	likely_pathogenic	0.5658	pathogenic	0.364	Stabilizing	0.908	D	0.793	deleterious	N	0.504552328	None	None	N
K/L	0.5925	likely_pathogenic	0.5488	ambiguous	0.364	Stabilizing	0.866	D	0.679	prob.neutral	None	None	None	None	N
K/M	0.4507	ambiguous	0.4096	ambiguous	0.51	Stabilizing	0.993	D	0.701	prob.neutral	None	None	None	None	N
K/N	0.6371	likely_pathogenic	0.576	pathogenic	0.097	Stabilizing	0.83	D	0.695	prob.neutral	N	0.465163813	None	None	N
K/P	0.797	likely_pathogenic	0.7475	pathogenic	0.211	Stabilizing	0.929	D	0.708	prob.delet.	None	None	None	None	N
K/Q	0.1794	likely_benign	0.1651	benign	-0.209	Destabilizing	0.83	D	0.692	prob.neutral	N	0.480825759	None	None	N
K/R	0.0649	likely_benign	0.0673	benign	-0.07	Destabilizing	0.01	N	0.289	neutral	N	0.468956845	None	None	N
K/S	0.5507	ambiguous	0.4938	ambiguous	-0.445	Destabilizing	0.648	D	0.592	neutral	None	None	None	None	N
K/T	0.3797	ambiguous	0.3197	benign	-0.281	Destabilizing	0.83	D	0.681	prob.neutral	N	0.475012408	None	None	N
K/V	0.5373	ambiguous	0.474	ambiguous	0.211	Stabilizing	0.866	D	0.736	prob.delet.	None	None	None	None	N
K/W	0.8257	likely_pathogenic	0.8107	pathogenic	-0.387	Destabilizing	0.993	D	0.793	deleterious	None	None	None	None	N
K/Y	0.7797	likely_pathogenic	0.75	pathogenic	-0.008	Destabilizing	0.929	D	0.779	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.