TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7346	22261;22262;22263	chr2:178722863;178722862;178722861	chr2:179587590;179587589;179587588
N2AB	7029	21310;21311;21312	chr2:178722863;178722862;178722861	chr2:179587590;179587589;179587588
N2A	6102	18529;18530;18531	chr2:178722863;178722862;178722861	chr2:179587590;179587589;179587588
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: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-58
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.118
• 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
V/A	rs1253051189	None	0.636	N	0.698	0.486	0.609565839933	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
V/A	rs1253051189	None	0.636	N	0.698	0.486	0.609565839933	gnomAD-4.0.0	2.47973E-06	None	None	None	None	N	None	5.34131E-05	0	None	0	0	None	0	0	0	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
V/A	0.5839	likely_pathogenic	0.6856	pathogenic	-1.954	Destabilizing	0.636	D	0.698	prob.neutral	N	0.49866733	None	None	N
V/C	0.968	likely_pathogenic	0.9742	pathogenic	-1.195	Destabilizing	0.998	D	0.791	deleterious	None	None	None	None	N
V/D	0.9899	likely_pathogenic	0.9948	pathogenic	-2.715	Highly Destabilizing	0.998	D	0.838	deleterious	D	0.573924875	None	None	N
V/E	0.9676	likely_pathogenic	0.9818	pathogenic	-2.423	Highly Destabilizing	0.681	D	0.576	neutral	None	None	None	None	N
V/F	0.6157	likely_pathogenic	0.6756	pathogenic	-1.098	Destabilizing	0.965	D	0.833	deleterious	D	0.56475973	None	None	N
V/G	0.8039	likely_pathogenic	0.8734	pathogenic	-2.543	Highly Destabilizing	0.99	D	0.836	deleterious	D	0.573924875	None	None	N
V/H	0.992	likely_pathogenic	0.9951	pathogenic	-2.496	Highly Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
V/I	0.0908	likely_benign	0.1042	benign	-0.266	Destabilizing	0.005	N	0.257	neutral	N	0.510516332	None	None	N
V/K	0.9811	likely_pathogenic	0.9884	pathogenic	-1.407	Destabilizing	0.998	D	0.811	deleterious	None	None	None	None	N
V/L	0.3022	likely_benign	0.383	ambiguous	-0.266	Destabilizing	0.002	N	0.315	neutral	D	0.547731348	None	None	N
V/M	0.4195	ambiguous	0.5116	ambiguous	-0.374	Destabilizing	0.963	D	0.719	prob.delet.	None	None	None	None	N
V/N	0.9771	likely_pathogenic	0.9869	pathogenic	-1.965	Destabilizing	0.994	D	0.858	deleterious	None	None	None	None	N
V/P	0.9839	likely_pathogenic	0.9895	pathogenic	-0.807	Destabilizing	0.998	D	0.836	deleterious	None	None	None	None	N
V/Q	0.9751	likely_pathogenic	0.9853	pathogenic	-1.651	Destabilizing	0.997	D	0.836	deleterious	None	None	None	None	N
V/R	0.9679	likely_pathogenic	0.9797	pathogenic	-1.527	Destabilizing	0.999	D	0.858	deleterious	None	None	None	None	N
V/S	0.9016	likely_pathogenic	0.9438	pathogenic	-2.51	Highly Destabilizing	0.998	D	0.817	deleterious	None	None	None	None	N
V/T	0.6787	likely_pathogenic	0.7697	pathogenic	-2.064	Highly Destabilizing	0.986	D	0.735	prob.delet.	None	None	None	None	N
V/W	0.988	likely_pathogenic	0.9929	pathogenic	-1.712	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
V/Y	0.9591	likely_pathogenic	0.9702	pathogenic	-1.293	Destabilizing	1.0	D	0.814	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.