TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10071	30436;30437;30438	chr2:178704159;178704158;178704157	chr2:179568886;179568885;179568884
N2AB	9754	29485;29486;29487	chr2:178704159;178704158;178704157	chr2:179568886;179568885;179568884
N2A	8827	26704;26705;26706	chr2:178704159;178704158;178704157	chr2:179568886;179568885;179568884
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-85
• Domain position: 83
• Structural Position: 174
• Q(SASA): 0.1026
• 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
L/R	rs879001616	-1.848	1.0	None	0.816	0.708	None	gnomAD-4.0.0	3.18278E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88665E-05	0	0	0	3.02352E-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
L/A	0.9744	likely_pathogenic	0.9838	pathogenic	-3.065	Highly Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
L/C	0.9718	likely_pathogenic	0.983	pathogenic	-2.44	Highly Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
L/D	0.9994	likely_pathogenic	0.9996	pathogenic	-3.774	Highly Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
L/E	0.9962	likely_pathogenic	0.9976	pathogenic	-3.549	Highly Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
L/F	0.8229	likely_pathogenic	0.9091	pathogenic	-1.842	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
L/G	0.9931	likely_pathogenic	0.9954	pathogenic	-3.592	Highly Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
L/H	0.9935	likely_pathogenic	0.9963	pathogenic	-3.023	Highly Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
L/I	0.2462	likely_benign	0.3464	ambiguous	-1.513	Destabilizing	0.999	D	0.541	neutral	None	None	None	None	N
L/K	0.9928	likely_pathogenic	0.9944	pathogenic	-2.574	Highly Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
L/M	0.4491	ambiguous	0.5767	pathogenic	-1.486	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
L/N	0.9957	likely_pathogenic	0.9971	pathogenic	-2.983	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
L/P	0.9977	likely_pathogenic	0.9989	pathogenic	-2.017	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
L/Q	0.9903	likely_pathogenic	0.9943	pathogenic	-2.843	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
L/R	0.9876	likely_pathogenic	0.9912	pathogenic	-2.148	Highly Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
L/S	0.9969	likely_pathogenic	0.9984	pathogenic	-3.596	Highly Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
L/T	0.9814	likely_pathogenic	0.9887	pathogenic	-3.242	Highly Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
L/V	0.385	ambiguous	0.536	ambiguous	-2.017	Highly Destabilizing	0.999	D	0.542	neutral	None	None	None	None	N
L/W	0.9741	likely_pathogenic	0.9888	pathogenic	-2.319	Highly Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
L/Y	0.9791	likely_pathogenic	0.9888	pathogenic	-2.134	Highly Destabilizing	1.0	D	0.815	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.