TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1141	3646;3647;3648	chr2:178781223;178781222;178781221	chr2:179645950;179645949;179645948
N2AB	1141	3646;3647;3648	chr2:178781223;178781222;178781221	chr2:179645950;179645949;179645948
N2A	1141	3646;3647;3648	chr2:178781223;178781222;178781221	chr2:179645950;179645949;179645948
N2B	1095	3508;3509;3510	chr2:178781223;178781222;178781221	chr2:179645950;179645949;179645948
Novex-1	1095	3508;3509;3510	chr2:178781223;178781222;178781221	chr2:179645950;179645949;179645948
Novex-2	1095	3508;3509;3510	chr2:178781223;178781222;178781221	chr2:179645950;179645949;179645948
Novex-3	1141	3646;3647;3648	chr2:178781223;178781222;178781221	chr2:179645950;179645949;179645948

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-4
• Domain position: 60
• Structural Position: 138
• Q(SASA): 0.0491
• 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/M	None	None	1.0	D	0.785	0.536	0.715311462823	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
L/A	0.9806	likely_pathogenic	0.9724	pathogenic	-2.214	Highly Destabilizing	0.999	D	0.748	deleterious	None	None	None	None	N
L/C	0.983	likely_pathogenic	0.9725	pathogenic	-1.359	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/D	0.9999	likely_pathogenic	0.9999	pathogenic	-3.007	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
L/E	0.9992	likely_pathogenic	0.9991	pathogenic	-2.69	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
L/F	0.894	likely_pathogenic	0.8581	pathogenic	-1.401	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
L/G	0.9968	likely_pathogenic	0.9955	pathogenic	-2.779	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
L/H	0.9983	likely_pathogenic	0.9981	pathogenic	-2.756	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
L/I	0.6129	likely_pathogenic	0.5281	ambiguous	-0.501	Destabilizing	0.999	D	0.648	neutral	None	None	None	None	N
L/K	0.9986	likely_pathogenic	0.9986	pathogenic	-1.734	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
L/M	0.601	likely_pathogenic	0.5229	ambiguous	-0.706	Destabilizing	1.0	D	0.785	deleterious	D	0.663419089	None	None	N
L/N	0.9992	likely_pathogenic	0.9992	pathogenic	-2.525	Highly Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	N
L/P	0.9998	likely_pathogenic	0.9997	pathogenic	-1.065	Destabilizing	1.0	D	0.905	deleterious	D	0.793669378	None	None	N
L/Q	0.9979	likely_pathogenic	0.9975	pathogenic	-2.078	Highly Destabilizing	1.0	D	0.908	deleterious	D	0.793669378	None	None	N
L/R	0.9969	likely_pathogenic	0.9967	pathogenic	-2.083	Highly Destabilizing	1.0	D	0.899	deleterious	D	0.793669378	None	None	N
L/S	0.9993	likely_pathogenic	0.9991	pathogenic	-2.921	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
L/T	0.9948	likely_pathogenic	0.9925	pathogenic	-2.437	Highly Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
L/V	0.6854	likely_pathogenic	0.5863	pathogenic	-1.065	Destabilizing	0.999	D	0.655	neutral	D	0.645088725	None	None	N
L/W	0.9951	likely_pathogenic	0.9932	pathogenic	-1.751	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
L/Y	0.993	likely_pathogenic	0.9918	pathogenic	-1.551	Destabilizing	1.0	D	0.855	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.