TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17987	54184;54185;54186	chr2:178605218;178605217;178605216	chr2:179469945;179469944;179469943
N2AB	16346	49261;49262;49263	chr2:178605218;178605217;178605216	chr2:179469945;179469944;179469943
N2A	15419	46480;46481;46482	chr2:178605218;178605217;178605216	chr2:179469945;179469944;179469943
N2B	8922	26989;26990;26991	chr2:178605218;178605217;178605216	chr2:179469945;179469944;179469943
Novex-1	9047	27364;27365;27366	chr2:178605218;178605217;178605216	chr2:179469945;179469944;179469943
Novex-2	9114	27565;27566;27567	chr2:178605218;178605217;178605216	chr2:179469945;179469944;179469943
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: Ig-114
• Domain position: 20
• Structural Position: 31
• Q(SASA): 0.3763
• Predicted PPI site: N

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/T	rs1315555738	-0.78	1.0	N	0.745	0.418	0.619976913611	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.01E-06	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
P/A	0.1591	likely_benign	0.1179	benign	-1.306	Destabilizing	1.0	D	0.705	prob.neutral	N	0.511873408	None	None	N
P/C	0.7598	likely_pathogenic	0.6899	pathogenic	-0.843	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
P/D	0.7297	likely_pathogenic	0.67	pathogenic	-1.037	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
P/E	0.5614	ambiguous	0.46	ambiguous	-1.052	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
P/F	0.7135	likely_pathogenic	0.6241	pathogenic	-1.021	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
P/G	0.5558	ambiguous	0.4754	ambiguous	-1.605	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
P/H	0.5066	ambiguous	0.4057	ambiguous	-1.132	Destabilizing	1.0	D	0.741	deleterious	N	0.505814228	None	None	N
P/I	0.4825	ambiguous	0.3845	ambiguous	-0.598	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
P/K	0.6145	likely_pathogenic	0.4958	ambiguous	-1.118	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
P/L	0.2516	likely_benign	0.1854	benign	-0.598	Destabilizing	1.0	D	0.769	deleterious	N	0.512566842	None	None	N
P/M	0.528	ambiguous	0.4221	ambiguous	-0.469	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
P/N	0.6761	likely_pathogenic	0.5802	pathogenic	-0.871	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
P/Q	0.44	ambiguous	0.3294	benign	-1.044	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
P/R	0.4786	ambiguous	0.3698	ambiguous	-0.589	Destabilizing	1.0	D	0.763	deleterious	N	0.492922288	None	None	N
P/S	0.322	likely_benign	0.236	benign	-1.369	Destabilizing	1.0	D	0.752	deleterious	N	0.488015114	None	None	N
P/T	0.2458	likely_benign	0.1757	benign	-1.273	Destabilizing	1.0	D	0.745	deleterious	N	0.475912608	None	None	N
P/V	0.3387	likely_benign	0.2618	benign	-0.798	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
P/W	0.8772	likely_pathogenic	0.8323	pathogenic	-1.196	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
P/Y	0.7247	likely_pathogenic	0.65	pathogenic	-0.907	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N

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.