TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28155	84688;84689;84690	chr2:178561669;178561668;178561667	chr2:179426396;179426395;179426394
N2AB	26514	79765;79766;79767	chr2:178561669;178561668;178561667	chr2:179426396;179426395;179426394
N2A	25587	76984;76985;76986	chr2:178561669;178561668;178561667	chr2:179426396;179426395;179426394
N2B	19090	57493;57494;57495	chr2:178561669;178561668;178561667	chr2:179426396;179426395;179426394
Novex-1	19215	57868;57869;57870	chr2:178561669;178561668;178561667	chr2:179426396;179426395;179426394
Novex-2	19282	58069;58070;58071	chr2:178561669;178561668;178561667	chr2:179426396;179426395;179426394
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: Fn3-93
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.1687
• 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/S	None	None	1.0	D	0.772	0.517	0.579429855601	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.7626	likely_pathogenic	0.7936	pathogenic	-1.295	Destabilizing	0.999	D	0.813	deleterious	N	0.521702894	None	None	N
P/C	0.9825	likely_pathogenic	0.9881	pathogenic	-1.785	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
P/D	0.9993	likely_pathogenic	0.9995	pathogenic	-3.098	Highly Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
P/E	0.9977	likely_pathogenic	0.9983	pathogenic	-3.066	Highly Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
P/F	0.9993	likely_pathogenic	0.9996	pathogenic	-1.071	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
P/G	0.9935	likely_pathogenic	0.9942	pathogenic	-1.592	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
P/H	0.9971	likely_pathogenic	0.998	pathogenic	-1.096	Destabilizing	1.0	D	0.735	deleterious	None	None	None	None	N
P/I	0.9709	likely_pathogenic	0.989	pathogenic	-0.55	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
P/K	0.998	likely_pathogenic	0.9986	pathogenic	-1.327	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
P/L	0.9357	likely_pathogenic	0.9672	pathogenic	-0.55	Destabilizing	1.0	D	0.835	deleterious	D	0.536337655	None	None	N
P/M	0.9919	likely_pathogenic	0.9957	pathogenic	-0.736	Destabilizing	1.0	D	0.733	deleterious	None	None	None	None	N
P/N	0.9991	likely_pathogenic	0.9994	pathogenic	-1.6	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
P/Q	0.9947	likely_pathogenic	0.9962	pathogenic	-1.807	Destabilizing	1.0	D	0.825	deleterious	D	0.549214898	None	None	N
P/R	0.9921	likely_pathogenic	0.994	pathogenic	-0.853	Destabilizing	1.0	D	0.806	deleterious	D	0.548707919	None	None	N
P/S	0.9717	likely_pathogenic	0.9756	pathogenic	-1.879	Destabilizing	1.0	D	0.772	deleterious	D	0.525070255	None	None	N
P/T	0.9613	likely_pathogenic	0.9722	pathogenic	-1.749	Destabilizing	1.0	D	0.779	deleterious	D	0.548707919	None	None	N
P/V	0.9205	likely_pathogenic	0.9614	pathogenic	-0.769	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
P/W	0.9998	likely_pathogenic	0.9999	pathogenic	-1.395	Destabilizing	1.0	D	0.731	deleterious	None	None	None	None	N
P/Y	0.9994	likely_pathogenic	0.9996	pathogenic	-1.023	Destabilizing	1.0	D	0.812	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.