TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2940	9043;9044;9045	chr2:178769763;178769762;178769761	chr2:179634490;179634489;179634488
N2AB	2940	9043;9044;9045	chr2:178769763;178769762;178769761	chr2:179634490;179634489;179634488
N2A	2940	9043;9044;9045	chr2:178769763;178769762;178769761	chr2:179634490;179634489;179634488
N2B	2894	8905;8906;8907	chr2:178769763;178769762;178769761	chr2:179634490;179634489;179634488
Novex-1	2894	8905;8906;8907	chr2:178769763;178769762;178769761	chr2:179634490;179634489;179634488
Novex-2	2894	8905;8906;8907	chr2:178769763;178769762;178769761	chr2:179634490;179634489;179634488
Novex-3	2940	9043;9044;9045	chr2:178769763;178769762;178769761	chr2:179634490;179634489;179634488

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-19
• Domain position: 59
• Structural Position: 140
• Q(SASA): 0.0823
• 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
I/S	None	None	1.0	D	0.837	0.898	0.914331358099	gnomAD-4.0.0	1.59048E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-05	0
I/V	rs939966359	None	0.993	D	0.385	0.458	0.767465642132	gnomAD-4.0.0	1.59048E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85652E-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
I/A	0.9886	likely_pathogenic	0.9888	pathogenic	-2.852	Highly Destabilizing	0.999	D	0.672	neutral	None	None	None	None	N
I/C	0.9874	likely_pathogenic	0.9892	pathogenic	-2.334	Highly Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
I/D	0.9997	likely_pathogenic	0.9996	pathogenic	-3.361	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
I/E	0.9988	likely_pathogenic	0.9987	pathogenic	-3.046	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
I/F	0.8814	likely_pathogenic	0.848	pathogenic	-1.709	Destabilizing	1.0	D	0.792	deleterious	D	0.697231272	None	None	N
I/G	0.9989	likely_pathogenic	0.9989	pathogenic	-3.488	Highly Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
I/H	0.9975	likely_pathogenic	0.9975	pathogenic	-3.096	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
I/K	0.9963	likely_pathogenic	0.996	pathogenic	-2.176	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
I/L	0.5087	ambiguous	0.4964	ambiguous	-0.955	Destabilizing	0.993	D	0.412	neutral	D	0.6088733	None	None	N
I/M	0.6337	likely_pathogenic	0.6179	pathogenic	-1.171	Destabilizing	1.0	D	0.746	deleterious	D	0.725693976	None	None	N
I/N	0.9948	likely_pathogenic	0.9945	pathogenic	-2.801	Highly Destabilizing	1.0	D	0.88	deleterious	D	0.780881292	None	None	N
I/P	0.9992	likely_pathogenic	0.999	pathogenic	-1.576	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
I/Q	0.9973	likely_pathogenic	0.9971	pathogenic	-2.486	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
I/R	0.9939	likely_pathogenic	0.9932	pathogenic	-2.144	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
I/S	0.9925	likely_pathogenic	0.9926	pathogenic	-3.497	Highly Destabilizing	1.0	D	0.837	deleterious	D	0.780881292	None	None	N
I/T	0.9869	likely_pathogenic	0.988	pathogenic	-3.007	Highly Destabilizing	1.0	D	0.781	deleterious	D	0.781086047	None	None	N
I/V	0.1987	likely_benign	0.2174	benign	-1.576	Destabilizing	0.993	D	0.385	neutral	D	0.547485435	None	None	N
I/W	0.9978	likely_pathogenic	0.9977	pathogenic	-2.117	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
I/Y	0.9912	likely_pathogenic	0.9901	pathogenic	-1.88	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.