TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7727	23404;23405;23406	chr2:178720583;178720582;178720581	chr2:179585310;179585309;179585308
N2AB	7410	22453;22454;22455	chr2:178720583;178720582;178720581	chr2:179585310;179585309;179585308
N2A	6483	19672;19673;19674	chr2:178720583;178720582;178720581	chr2:179585310;179585309;179585308
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-62
• Domain position: 26
• Structural Position: 40
• Q(SASA): 0.3136
• 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	rs763907919	0.043	1.0	D	0.828	0.787	0.836363966263	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
G/E	rs763907919	0.043	1.0	D	0.828	0.787	0.836363966263	gnomAD-4.0.0	3.18505E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.72033E-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	0.9241	likely_pathogenic	0.9136	pathogenic	-0.33	Destabilizing	1.0	D	0.781	deleterious	D	0.567179587	None	None	I
G/C	0.9939	likely_pathogenic	0.9928	pathogenic	-0.625	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
G/D	0.9957	likely_pathogenic	0.9945	pathogenic	-0.485	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
G/E	0.9974	likely_pathogenic	0.9968	pathogenic	-0.5	Destabilizing	1.0	D	0.828	deleterious	D	0.622738378	None	None	I
G/F	0.999	likely_pathogenic	0.9988	pathogenic	-0.628	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	I
G/H	0.9993	likely_pathogenic	0.999	pathogenic	-0.764	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
G/I	0.9981	likely_pathogenic	0.9977	pathogenic	0.065	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
G/K	0.9991	likely_pathogenic	0.9988	pathogenic	-0.765	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	I
G/L	0.998	likely_pathogenic	0.9977	pathogenic	0.065	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
G/M	0.999	likely_pathogenic	0.9989	pathogenic	-0.214	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	I
G/N	0.9974	likely_pathogenic	0.9962	pathogenic	-0.607	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
G/P	0.9995	likely_pathogenic	0.9993	pathogenic	-0.026	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	I
G/Q	0.9982	likely_pathogenic	0.9976	pathogenic	-0.662	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
G/R	0.9969	likely_pathogenic	0.9958	pathogenic	-0.589	Destabilizing	1.0	D	0.82	deleterious	D	0.638211252	None	None	I
G/S	0.9452	likely_pathogenic	0.9258	pathogenic	-0.882	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
G/T	0.9938	likely_pathogenic	0.992	pathogenic	-0.791	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
G/V	0.995	likely_pathogenic	0.9942	pathogenic	-0.026	Destabilizing	1.0	D	0.795	deleterious	D	0.647730003	None	None	I
G/W	0.9984	likely_pathogenic	0.9976	pathogenic	-1.029	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
G/Y	0.9991	likely_pathogenic	0.9988	pathogenic	-0.527	Destabilizing	1.0	D	0.759	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.