TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26620	80083;80084;80085	chr2:178566274;178566273;178566272	chr2:179431001;179431000;179430999
N2AB	24979	75160;75161;75162	chr2:178566274;178566273;178566272	chr2:179431001;179431000;179430999
N2A	24052	72379;72380;72381	chr2:178566274;178566273;178566272	chr2:179431001;179431000;179430999
N2B	17555	52888;52889;52890	chr2:178566274;178566273;178566272	chr2:179431001;179431000;179430999
Novex-1	17680	53263;53264;53265	chr2:178566274;178566273;178566272	chr2:179431001;179431000;179430999
Novex-2	17747	53464;53465;53466	chr2:178566274;178566273;178566272	chr2:179431001;179431000;179430999
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: Ig-138
• Domain position: 27
• Structural Position: 42
• Q(SASA): 0.5772
• Predicted PPI site: I

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/L	rs1260392231	None	1.0	D	0.761	0.728	0.891535782347	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
P/L	rs1260392231	None	1.0	D	0.761	0.728	0.891535782347	gnomAD-4.0.0	3.04525E-06	None	None	None	None	I	None	3.49724E-05	0	None	0	0	None	0	0	0	0	3.40252E-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	0.9576	likely_pathogenic	0.9688	pathogenic	-0.475	Destabilizing	1.0	D	0.741	deleterious	D	0.566887167	None	None	I
P/C	0.9956	likely_pathogenic	0.9973	pathogenic	-0.554	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
P/D	0.9934	likely_pathogenic	0.9944	pathogenic	-0.222	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
P/E	0.9916	likely_pathogenic	0.9932	pathogenic	-0.354	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
P/F	0.9976	likely_pathogenic	0.9983	pathogenic	-0.835	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
P/G	0.9872	likely_pathogenic	0.99	pathogenic	-0.581	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
P/H	0.9894	likely_pathogenic	0.991	pathogenic	-0.237	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
P/I	0.9825	likely_pathogenic	0.9861	pathogenic	-0.356	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
P/K	0.9912	likely_pathogenic	0.992	pathogenic	-0.311	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
P/L	0.9525	likely_pathogenic	0.9632	pathogenic	-0.356	Destabilizing	1.0	D	0.761	deleterious	D	0.599473705	None	None	I
P/M	0.988	likely_pathogenic	0.9913	pathogenic	-0.275	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	I
P/N	0.991	likely_pathogenic	0.9931	pathogenic	-0.032	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
P/Q	0.9871	likely_pathogenic	0.9897	pathogenic	-0.314	Destabilizing	1.0	D	0.773	deleterious	D	0.578408056	None	None	I
P/R	0.9839	likely_pathogenic	0.9848	pathogenic	0.195	Stabilizing	1.0	D	0.779	deleterious	D	0.644342203	None	None	I
P/S	0.9875	likely_pathogenic	0.9912	pathogenic	-0.385	Destabilizing	1.0	D	0.745	deleterious	D	0.577901077	None	None	I
P/T	0.9683	likely_pathogenic	0.976	pathogenic	-0.42	Destabilizing	1.0	D	0.742	deleterious	D	0.628090678	None	None	I
P/V	0.9688	likely_pathogenic	0.9745	pathogenic	-0.362	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
P/W	0.9987	likely_pathogenic	0.9991	pathogenic	-0.894	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
P/Y	0.9955	likely_pathogenic	0.9969	pathogenic	-0.58	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I

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.