TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33101	99526;99527;99528	chr2:178537906;178537905;178537904	chr2:179402633;179402632;179402631
N2AB	31460	94603;94604;94605	chr2:178537906;178537905;178537904	chr2:179402633;179402632;179402631
N2A	30533	91822;91823;91824	chr2:178537906;178537905;178537904	chr2:179402633;179402632;179402631
N2B	24036	72331;72332;72333	chr2:178537906;178537905;178537904	chr2:179402633;179402632;179402631
Novex-1	24161	72706;72707;72708	chr2:178537906;178537905;178537904	chr2:179402633;179402632;179402631
Novex-2	24228	72907;72908;72909	chr2:178537906;178537905;178537904	chr2:179402633;179402632;179402631
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-156
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.1249
• 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	None	None	1.0	D	0.813	0.651	0.916515394442	gnomAD-4.0.0	1.60306E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.44238E-05	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	0.5638	ambiguous	0.5832	pathogenic	-1.588	Destabilizing	1.0	D	0.733	prob.delet.	D	0.613298195	None	None	N
P/C	0.9748	likely_pathogenic	0.9794	pathogenic	-1.209	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
P/D	0.9984	likely_pathogenic	0.9986	pathogenic	-1.498	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
P/E	0.9956	likely_pathogenic	0.9956	pathogenic	-1.5	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
P/F	0.9986	likely_pathogenic	0.9986	pathogenic	-1.271	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
P/G	0.9759	likely_pathogenic	0.9811	pathogenic	-1.889	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
P/H	0.9963	likely_pathogenic	0.9956	pathogenic	-1.324	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
P/I	0.9714	likely_pathogenic	0.9698	pathogenic	-0.855	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
P/K	0.9971	likely_pathogenic	0.9967	pathogenic	-1.157	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
P/L	0.9265	likely_pathogenic	0.9165	pathogenic	-0.855	Destabilizing	1.0	D	0.813	deleterious	D	0.62298839	None	None	N
P/M	0.9882	likely_pathogenic	0.9875	pathogenic	-0.77	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
P/N	0.9975	likely_pathogenic	0.9975	pathogenic	-0.99	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
P/Q	0.9927	likely_pathogenic	0.9917	pathogenic	-1.21	Destabilizing	1.0	D	0.805	deleterious	D	0.639441719	None	None	N
P/R	0.9907	likely_pathogenic	0.9893	pathogenic	-0.645	Destabilizing	1.0	D	0.792	deleterious	D	0.639441719	None	None	N
P/S	0.9538	likely_pathogenic	0.9557	pathogenic	-1.531	Destabilizing	1.0	D	0.817	deleterious	D	0.639038111	None	None	N
P/T	0.9325	likely_pathogenic	0.9286	pathogenic	-1.43	Destabilizing	1.0	D	0.815	deleterious	D	0.639239915	None	None	N
P/V	0.913	likely_pathogenic	0.9087	pathogenic	-1.066	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
P/W	0.9996	likely_pathogenic	0.9997	pathogenic	-1.397	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
P/Y	0.9992	likely_pathogenic	0.9991	pathogenic	-1.11	Destabilizing	1.0	D	0.777	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.