TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4737	14434;14435;14436	chr2:178738244;178738243;178738242	chr2:179602971;179602970;179602969
N2AB	4420	13483;13484;13485	chr2:178738244;178738243;178738242	chr2:179602971;179602970;179602969
N2A	3493	10702;10703;10704	chr2:178738244;178738243;178738242	chr2:179602971;179602970;179602969
N2B	4374	13345;13346;13347	chr2:178738244;178738243;178738242	chr2:179602971;179602970;179602969
Novex-1	4499	13720;13721;13722	chr2:178738244;178738243;178738242	chr2:179602971;179602970;179602969
Novex-2	4566	13921;13922;13923	chr2:178738244;178738243;178738242	chr2:179602971;179602970;179602969
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-30
• Domain position: 38
• Structural Position: 52
• Q(SASA): 0.6115
• 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
G/C	None	None	1.0	D	0.764	0.536	0.647102547044	gnomAD-4.0.0	1.59177E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85858E-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
G/A	0.4342	ambiguous	0.6273	pathogenic	-0.286	Destabilizing	0.998	D	0.47	neutral	D	0.630992762	None	None	I
G/C	0.6997	likely_pathogenic	0.7936	pathogenic	-0.934	Destabilizing	1.0	D	0.764	deleterious	D	0.74997377	None	None	I
G/D	0.417	ambiguous	0.6062	pathogenic	-0.519	Destabilizing	1.0	D	0.62	neutral	N	0.502744456	None	None	I
G/E	0.4782	ambiguous	0.693	pathogenic	-0.66	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	I
G/F	0.9263	likely_pathogenic	0.9642	pathogenic	-0.915	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
G/H	0.744	likely_pathogenic	0.8635	pathogenic	-0.382	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
G/I	0.8998	likely_pathogenic	0.9567	pathogenic	-0.403	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
G/K	0.7175	likely_pathogenic	0.8441	pathogenic	-0.814	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	I
G/L	0.8743	likely_pathogenic	0.9383	pathogenic	-0.403	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
G/M	0.8893	likely_pathogenic	0.9469	pathogenic	-0.626	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
G/N	0.4194	ambiguous	0.6069	pathogenic	-0.529	Destabilizing	1.0	D	0.636	neutral	None	None	None	None	I
G/P	0.9865	likely_pathogenic	0.9922	pathogenic	-0.333	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
G/Q	0.5555	ambiguous	0.7358	pathogenic	-0.766	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
G/R	0.5482	ambiguous	0.7149	pathogenic	-0.375	Destabilizing	1.0	D	0.709	prob.delet.	D	0.630859361	None	None	I
G/S	0.1888	likely_benign	0.3117	benign	-0.689	Destabilizing	0.991	D	0.563	neutral	D	0.582363206	None	None	I
G/T	0.593	likely_pathogenic	0.7752	pathogenic	-0.754	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	I
G/V	0.8059	likely_pathogenic	0.9118	pathogenic	-0.333	Destabilizing	1.0	D	0.732	prob.delet.	D	0.715862877	None	None	I
G/W	0.8276	likely_pathogenic	0.8993	pathogenic	-1.073	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	I
G/Y	0.8529	likely_pathogenic	0.9226	pathogenic	-0.732	Destabilizing	1.0	D	0.763	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.