TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8332	25219;25220;25221	chr2:178718012;178718011;178718010	chr2:179582739;179582738;179582737
N2AB	8015	24268;24269;24270	chr2:178718012;178718011;178718010	chr2:179582739;179582738;179582737
N2A	7088	21487;21488;21489	chr2:178718012;178718011;178718010	chr2:179582739;179582738;179582737
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: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-68
• Domain position: 69
• Structural Position: 152
• Q(SASA): 0.2195
• 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/E	rs2077756630	None	1.0	D	0.839	0.699	0.883990867487	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
G/E	rs2077756630	None	1.0	D	0.839	0.699	0.883990867487	gnomAD-4.0.0	6.57212E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47024E-05	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	0.4114	ambiguous	0.4663	ambiguous	-0.607	Destabilizing	0.999	D	0.787	deleterious	D	0.589108403	None	None	I
G/C	0.8408	likely_pathogenic	0.9062	pathogenic	-0.728	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
G/D	0.8499	likely_pathogenic	0.9268	pathogenic	-1.163	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
G/E	0.9201	likely_pathogenic	0.9633	pathogenic	-1.164	Destabilizing	1.0	D	0.839	deleterious	D	0.679913347	None	None	I
G/F	0.9765	likely_pathogenic	0.9882	pathogenic	-0.786	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
G/H	0.9721	likely_pathogenic	0.9892	pathogenic	-1.392	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
G/I	0.9768	likely_pathogenic	0.9889	pathogenic	-0.045	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
G/K	0.9776	likely_pathogenic	0.9908	pathogenic	-1.254	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	I
G/L	0.9613	likely_pathogenic	0.9771	pathogenic	-0.045	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	I
G/M	0.9736	likely_pathogenic	0.9851	pathogenic	-0.045	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
G/N	0.9303	likely_pathogenic	0.9695	pathogenic	-1.007	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	I
G/P	0.997	likely_pathogenic	0.9984	pathogenic	-0.189	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	I
G/Q	0.9383	likely_pathogenic	0.9718	pathogenic	-1.083	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	I
G/R	0.9333	likely_pathogenic	0.9691	pathogenic	-1.038	Destabilizing	1.0	D	0.829	deleterious	D	0.679913347	None	None	I
G/S	0.4089	ambiguous	0.5892	pathogenic	-1.291	Destabilizing	0.997	D	0.707	prob.neutral	None	None	None	None	I
G/T	0.8657	likely_pathogenic	0.9288	pathogenic	-1.203	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	I
G/V	0.9356	likely_pathogenic	0.9657	pathogenic	-0.189	Destabilizing	1.0	D	0.797	deleterious	D	0.679913347	None	None	I
G/W	0.9552	likely_pathogenic	0.9822	pathogenic	-1.305	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
G/Y	0.9726	likely_pathogenic	0.9885	pathogenic	-0.814	Destabilizing	1.0	D	0.812	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.