TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9922	29989;29990;29991	chr2:178704708;178704707;178704706	chr2:179569435;179569434;179569433
N2AB	9605	29038;29039;29040	chr2:178704708;178704707;178704706	chr2:179569435;179569434;179569433
N2A	8678	26257;26258;26259	chr2:178704708;178704707;178704706	chr2:179569435;179569434;179569433
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: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-84
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.1699
• 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
D/H	None	None	0.896	None	0.541	0.319	0.342865806769	gnomAD-4.0.0	2.05623E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.6998E-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
D/A	0.4732	ambiguous	0.4127	ambiguous	-0.802	Destabilizing	0.379	N	0.534	neutral	None	None	None	None	N
D/C	0.9169	likely_pathogenic	0.9064	pathogenic	-0.569	Destabilizing	0.992	D	0.609	neutral	None	None	None	None	N
D/E	0.394	ambiguous	0.4041	ambiguous	-0.885	Destabilizing	0.001	N	0.204	neutral	None	None	None	None	N
D/F	0.8985	likely_pathogenic	0.8777	pathogenic	-0.614	Destabilizing	0.972	D	0.591	neutral	None	None	None	None	N
D/G	0.7394	likely_pathogenic	0.6012	pathogenic	-1.185	Destabilizing	0.549	D	0.517	neutral	None	None	None	None	N
D/H	0.6779	likely_pathogenic	0.627	pathogenic	-0.979	Destabilizing	0.896	D	0.541	neutral	None	None	None	None	N
D/I	0.7169	likely_pathogenic	0.6567	pathogenic	0.232	Stabilizing	0.92	D	0.575	neutral	None	None	None	None	N
D/K	0.86	likely_pathogenic	0.8091	pathogenic	-1.102	Destabilizing	0.447	N	0.517	neutral	None	None	None	None	N
D/L	0.751	likely_pathogenic	0.7324	pathogenic	0.232	Stabilizing	0.85	D	0.565	neutral	None	None	None	None	N
D/M	0.9138	likely_pathogenic	0.9094	pathogenic	0.787	Stabilizing	0.992	D	0.581	neutral	None	None	None	None	N
D/N	0.2566	likely_benign	0.2159	benign	-1.354	Destabilizing	0.549	D	0.504	neutral	None	None	None	None	N
D/P	0.9937	likely_pathogenic	0.9849	pathogenic	-0.089	Destabilizing	0.92	D	0.52	neutral	None	None	None	None	N
D/Q	0.7618	likely_pathogenic	0.7316	pathogenic	-1.138	Destabilizing	0.447	N	0.49	neutral	None	None	None	None	N
D/R	0.8573	likely_pathogenic	0.8055	pathogenic	-1.018	Destabilizing	0.85	D	0.545	neutral	None	None	None	None	N
D/S	0.3882	ambiguous	0.3362	benign	-1.81	Destabilizing	0.447	N	0.538	neutral	None	None	None	None	N
D/T	0.6478	likely_pathogenic	0.5701	pathogenic	-1.483	Destabilizing	0.617	D	0.495	neutral	None	None	None	None	N
D/V	0.5357	ambiguous	0.4728	ambiguous	-0.089	Destabilizing	0.81	D	0.571	neutral	None	None	None	None	N
D/W	0.9822	likely_pathogenic	0.9783	pathogenic	-0.644	Destabilizing	0.992	D	0.609	neutral	None	None	None	None	N
D/Y	0.6514	likely_pathogenic	0.5672	pathogenic	-0.441	Destabilizing	0.963	D	0.59	neutral	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.