TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21645	65158;65159;65160	chr2:178584708;178584707;178584706	chr2:179449435;179449434;179449433
N2AB	20004	60235;60236;60237	chr2:178584708;178584707;178584706	chr2:179449435;179449434;179449433
N2A	19077	57454;57455;57456	chr2:178584708;178584707;178584706	chr2:179449435;179449434;179449433
N2B	12580	37963;37964;37965	chr2:178584708;178584707;178584706	chr2:179449435;179449434;179449433
Novex-1	12705	38338;38339;38340	chr2:178584708;178584707;178584706	chr2:179449435;179449434;179449433
Novex-2	12772	38539;38540;38541	chr2:178584708;178584707;178584706	chr2:179449435;179449434;179449433
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-44
• Domain position: 87
• Structural Position: 120
• Q(SASA): 0.2376
• 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
P/L	None	None	0.993	N	0.744	0.459	None	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
P/S	rs1553632774	None	0.987	N	0.682	0.402	0.324986149311	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/S	rs1553632774	None	0.987	N	0.682	0.402	0.324986149311	gnomAD-4.0.0	2.03023E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.205E-06	0	3.40252E-05

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
P/A	0.1009	likely_benign	0.0943	benign	-1.769	Destabilizing	0.117	N	0.432	neutral	N	0.476088818	None	None	I
P/C	0.6294	likely_pathogenic	0.6077	pathogenic	-1.104	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
P/D	0.8951	likely_pathogenic	0.8806	pathogenic	-1.917	Destabilizing	0.998	D	0.728	prob.delet.	None	None	None	None	I
P/E	0.8154	likely_pathogenic	0.7994	pathogenic	-1.9	Destabilizing	0.995	D	0.721	prob.delet.	None	None	None	None	I
P/F	0.6979	likely_pathogenic	0.6542	pathogenic	-1.319	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	I
P/G	0.4013	ambiguous	0.3669	ambiguous	-2.096	Highly Destabilizing	0.966	D	0.656	neutral	None	None	None	None	I
P/H	0.553	ambiguous	0.5198	ambiguous	-1.583	Destabilizing	1.0	D	0.802	deleterious	D	0.531619805	None	None	I
P/I	0.6839	likely_pathogenic	0.675	pathogenic	-0.948	Destabilizing	0.995	D	0.789	deleterious	None	None	None	None	I
P/K	0.9017	likely_pathogenic	0.8961	pathogenic	-1.481	Destabilizing	0.995	D	0.729	prob.delet.	None	None	None	None	I
P/L	0.5455	ambiguous	0.5322	ambiguous	-0.948	Destabilizing	0.993	D	0.744	deleterious	N	0.511234144	None	None	I
P/M	0.6636	likely_pathogenic	0.6375	pathogenic	-0.701	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	I
P/N	0.7642	likely_pathogenic	0.7212	pathogenic	-1.32	Destabilizing	0.998	D	0.753	deleterious	None	None	None	None	I
P/Q	0.674	likely_pathogenic	0.6451	pathogenic	-1.508	Destabilizing	0.998	D	0.763	deleterious	None	None	None	None	I
P/R	0.8399	likely_pathogenic	0.8425	pathogenic	-0.888	Destabilizing	0.997	D	0.746	deleterious	N	0.515464106	None	None	I
P/S	0.2449	likely_benign	0.2095	benign	-1.811	Destabilizing	0.987	D	0.682	prob.neutral	N	0.503347333	None	None	I
P/T	0.3291	likely_benign	0.3045	benign	-1.698	Destabilizing	0.993	D	0.705	prob.neutral	D	0.530859337	None	None	I
P/V	0.4972	ambiguous	0.4905	ambiguous	-1.19	Destabilizing	0.99	D	0.678	prob.neutral	None	None	None	None	I
P/W	0.862	likely_pathogenic	0.8535	pathogenic	-1.543	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
P/Y	0.6723	likely_pathogenic	0.6324	pathogenic	-1.276	Destabilizing	1.0	D	0.837	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.