TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18032	54319;54320;54321	chr2:178605083;178605082;178605081	chr2:179469810;179469809;179469808
N2AB	16391	49396;49397;49398	chr2:178605083;178605082;178605081	chr2:179469810;179469809;179469808
N2A	15464	46615;46616;46617	chr2:178605083;178605082;178605081	chr2:179469810;179469809;179469808
N2B	8967	27124;27125;27126	chr2:178605083;178605082;178605081	chr2:179469810;179469809;179469808
Novex-1	9092	27499;27500;27501	chr2:178605083;178605082;178605081	chr2:179469810;179469809;179469808
Novex-2	9159	27700;27701;27702	chr2:178605083;178605082;178605081	chr2:179469810;179469809;179469808
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-114
• Domain position: 65
• Structural Position: 140
• Q(SASA): 0.1595
• 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/T	None	None	0.896	D	0.81	0.844	0.818036558674	gnomAD-4.0.0	1.59341E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02828E-05
I/V	rs1227589199	-1.488	0.437	D	0.421	0.522	0.528860544761	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
I/V	rs1227589199	-1.488	0.437	D	0.421	0.522	0.528860544761	gnomAD-4.0.0	3.1867E-06	None	None	None	None	N	None	0	4.57498E-05	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
I/A	0.9321	likely_pathogenic	0.9621	pathogenic	-2.847	Highly Destabilizing	0.919	D	0.719	prob.delet.	None	None	None	None	N
I/C	0.9159	likely_pathogenic	0.9493	pathogenic	-2.213	Highly Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
I/D	0.9904	likely_pathogenic	0.9955	pathogenic	-3.557	Highly Destabilizing	0.996	D	0.881	deleterious	None	None	None	None	N
I/E	0.9857	likely_pathogenic	0.993	pathogenic	-3.366	Highly Destabilizing	0.988	D	0.88	deleterious	None	None	None	None	N
I/F	0.2789	likely_benign	0.3791	ambiguous	-1.713	Destabilizing	0.968	D	0.758	deleterious	D	0.563898921	None	None	N
I/G	0.9872	likely_pathogenic	0.9938	pathogenic	-3.354	Highly Destabilizing	0.988	D	0.877	deleterious	None	None	None	None	N
I/H	0.9267	likely_pathogenic	0.9604	pathogenic	-2.845	Highly Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
I/K	0.9424	likely_pathogenic	0.9646	pathogenic	-2.486	Highly Destabilizing	0.976	D	0.879	deleterious	None	None	None	None	N
I/L	0.1273	likely_benign	0.1773	benign	-1.374	Destabilizing	0.011	N	0.3	neutral	D	0.578630049	None	None	N
I/M	0.2099	likely_benign	0.2944	benign	-1.268	Destabilizing	0.437	N	0.444	neutral	D	0.566513453	None	None	N
I/N	0.8558	likely_pathogenic	0.927	pathogenic	-2.768	Highly Destabilizing	0.984	D	0.877	deleterious	D	0.630842704	None	None	N
I/P	0.9927	likely_pathogenic	0.9949	pathogenic	-1.848	Destabilizing	0.996	D	0.875	deleterious	None	None	None	None	N
I/Q	0.9476	likely_pathogenic	0.9723	pathogenic	-2.681	Highly Destabilizing	0.988	D	0.875	deleterious	None	None	None	None	N
I/R	0.925	likely_pathogenic	0.9533	pathogenic	-2.023	Highly Destabilizing	0.988	D	0.879	deleterious	None	None	None	None	N
I/S	0.901	likely_pathogenic	0.947	pathogenic	-3.361	Highly Destabilizing	0.984	D	0.847	deleterious	D	0.614591178	None	None	N
I/T	0.9339	likely_pathogenic	0.9642	pathogenic	-3.046	Highly Destabilizing	0.896	D	0.81	deleterious	D	0.61418757	None	None	N
I/V	0.1524	likely_benign	0.1712	benign	-1.848	Destabilizing	0.437	N	0.421	neutral	D	0.577529127	None	None	N
I/W	0.9348	likely_pathogenic	0.9586	pathogenic	-2.191	Highly Destabilizing	0.999	D	0.856	deleterious	None	None	None	None	N
I/Y	0.8164	likely_pathogenic	0.8913	pathogenic	-1.979	Destabilizing	0.988	D	0.795	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.