TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28791	86596;86597;86598	chr2:178559761;178559760;178559759	chr2:179424488;179424487;179424486
N2AB	27150	81673;81674;81675	chr2:178559761;178559760;178559759	chr2:179424488;179424487;179424486
N2A	26223	78892;78893;78894	chr2:178559761;178559760;178559759	chr2:179424488;179424487;179424486
N2B	19726	59401;59402;59403	chr2:178559761;178559760;178559759	chr2:179424488;179424487;179424486
Novex-1	19851	59776;59777;59778	chr2:178559761;178559760;178559759	chr2:179424488;179424487;179424486
Novex-2	19918	59977;59978;59979	chr2:178559761;178559760;178559759	chr2:179424488;179424487;179424486
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-144
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.4515
• 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	N	0.735	0.372	0.383089235449	gnomAD-4.0.0	1.626E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.91552E-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	0.0837	likely_benign	0.0817	benign	-0.284	Destabilizing	1.0	D	0.703	prob.neutral	N	0.42461613	None	None	N
P/C	0.534	ambiguous	0.538	ambiguous	-0.615	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
P/D	0.3581	ambiguous	0.3531	ambiguous	-0.228	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
P/E	0.2203	likely_benign	0.217	benign	-0.357	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
P/F	0.513	ambiguous	0.504	ambiguous	-0.659	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
P/G	0.2661	likely_benign	0.2534	benign	-0.367	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
P/H	0.2465	likely_benign	0.2449	benign	-0.015	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
P/I	0.2928	likely_benign	0.2817	benign	-0.222	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
P/K	0.2889	likely_benign	0.2946	benign	-0.282	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
P/L	0.1243	likely_benign	0.1235	benign	-0.222	Destabilizing	1.0	D	0.735	prob.delet.	N	0.492110559	None	None	N
P/M	0.2468	likely_benign	0.2428	benign	-0.341	Destabilizing	1.0	D	0.668	neutral	None	None	None	None	N
P/N	0.2764	likely_benign	0.2675	benign	-0.037	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
P/Q	0.1604	likely_benign	0.1551	benign	-0.285	Destabilizing	1.0	D	0.701	prob.neutral	N	0.477853183	None	None	N
P/R	0.2438	likely_benign	0.2493	benign	0.194	Stabilizing	1.0	D	0.708	prob.delet.	N	0.502460839	None	None	N
P/S	0.1376	likely_benign	0.1331	benign	-0.355	Destabilizing	1.0	D	0.729	prob.delet.	N	0.461710294	None	None	N
P/T	0.1003	likely_benign	0.096	benign	-0.388	Destabilizing	1.0	D	0.718	prob.delet.	N	0.478026541	None	None	N
P/V	0.1969	likely_benign	0.1897	benign	-0.21	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
P/W	0.6641	likely_pathogenic	0.6687	pathogenic	-0.734	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
P/Y	0.4733	ambiguous	0.4654	ambiguous	-0.424	Destabilizing	1.0	D	0.681	prob.neutral	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.