TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22672	68239;68240;68241	chr2:178579016;178579015;178579014	chr2:179443743;179443742;179443741
N2AB	21031	63316;63317;63318	chr2:178579016;178579015;178579014	chr2:179443743;179443742;179443741
N2A	20104	60535;60536;60537	chr2:178579016;178579015;178579014	chr2:179443743;179443742;179443741
N2B	13607	41044;41045;41046	chr2:178579016;178579015;178579014	chr2:179443743;179443742;179443741
Novex-1	13732	41419;41420;41421	chr2:178579016;178579015;178579014	chr2:179443743;179443742;179443741
Novex-2	13799	41620;41621;41622	chr2:178579016;178579015;178579014	chr2:179443743;179443742;179443741
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: Fn3-52
• Domain position: 30
• Structural Position: 31
• Q(SASA): 0.4516
• 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	None	None	1.0	D	0.863	0.536	0.667787145914	gnomAD-4.0.0	1.59249E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43291E-05	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	0.9546	likely_pathogenic	0.9498	pathogenic	-0.33	Destabilizing	1.0	D	0.728	prob.delet.	N	0.516820459	None	None	I
G/C	0.984	likely_pathogenic	0.9822	pathogenic	-0.78	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	I
G/D	0.996	likely_pathogenic	0.9958	pathogenic	-0.347	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	I
G/E	0.9973	likely_pathogenic	0.9968	pathogenic	-0.497	Destabilizing	1.0	D	0.863	deleterious	D	0.534164246	None	None	I
G/F	0.9981	likely_pathogenic	0.998	pathogenic	-1.039	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
G/H	0.9977	likely_pathogenic	0.9974	pathogenic	-0.652	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	I
G/I	0.9978	likely_pathogenic	0.9972	pathogenic	-0.373	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	I
G/K	0.9975	likely_pathogenic	0.9969	pathogenic	-0.674	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	I
G/L	0.9968	likely_pathogenic	0.9965	pathogenic	-0.373	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	I
G/M	0.9983	likely_pathogenic	0.9981	pathogenic	-0.336	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
G/N	0.996	likely_pathogenic	0.9962	pathogenic	-0.275	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	I
G/P	0.9996	likely_pathogenic	0.9995	pathogenic	-0.323	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	I
G/Q	0.9964	likely_pathogenic	0.9961	pathogenic	-0.547	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
G/R	0.9892	likely_pathogenic	0.9872	pathogenic	-0.29	Destabilizing	1.0	D	0.851	deleterious	N	0.496816874	None	None	I
G/S	0.94	likely_pathogenic	0.9371	pathogenic	-0.493	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	I
G/T	0.9922	likely_pathogenic	0.9913	pathogenic	-0.563	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	I
G/V	0.9959	likely_pathogenic	0.995	pathogenic	-0.323	Destabilizing	1.0	D	0.839	deleterious	D	0.535685183	None	None	I
G/W	0.9947	likely_pathogenic	0.9935	pathogenic	-1.205	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
G/Y	0.9972	likely_pathogenic	0.9966	pathogenic	-0.832	Destabilizing	1.0	D	0.81	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.