TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17500	52723;52724;52725	chr2:178608385;178608384;178608383	chr2:179473112;179473111;179473110
N2AB	15859	47800;47801;47802	chr2:178608385;178608384;178608383	chr2:179473112;179473111;179473110
N2A	14932	45019;45020;45021	chr2:178608385;178608384;178608383	chr2:179473112;179473111;179473110
N2B	8435	25528;25529;25530	chr2:178608385;178608384;178608383	chr2:179473112;179473111;179473110
Novex-1	8560	25903;25904;25905	chr2:178608385;178608384;178608383	chr2:179473112;179473111;179473110
Novex-2	8627	26104;26105;26106	chr2:178608385;178608384;178608383	chr2:179473112;179473111;179473110
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-15
• Domain position: 31
• Structural Position: 34
• Q(SASA): 0.6143
• 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/H	rs1384771900	-0.3	1.0	N	0.624	0.498	0.59498951386	gnomAD-2.1.1	8.19E-06	None	None	None	None	I	None	0	0	None	0	5.73E-05	None	0	None	0	9.07E-06	0
P/S	None	None	0.995	N	0.628	0.391	0.311079019809	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

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	0.0877	likely_benign	0.0952	benign	-0.571	Destabilizing	0.619	D	0.433	neutral	N	0.508747385	None	None	I
P/C	0.5142	ambiguous	0.5976	pathogenic	-0.649	Destabilizing	1.0	D	0.634	neutral	None	None	None	None	I
P/D	0.3748	ambiguous	0.5002	ambiguous	-0.253	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	I
P/E	0.225	likely_benign	0.2955	benign	-0.365	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	I
P/F	0.5742	likely_pathogenic	0.6703	pathogenic	-0.769	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	I
P/G	0.3635	ambiguous	0.4087	ambiguous	-0.715	Destabilizing	0.988	D	0.61	neutral	None	None	None	None	I
P/H	0.2056	likely_benign	0.2609	benign	-0.256	Destabilizing	1.0	D	0.624	neutral	N	0.489249684	None	None	I
P/I	0.3174	likely_benign	0.398	ambiguous	-0.341	Destabilizing	0.999	D	0.671	neutral	None	None	None	None	I
P/K	0.2193	likely_benign	0.2908	benign	-0.444	Destabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	I
P/L	0.1506	likely_benign	0.1768	benign	-0.341	Destabilizing	0.998	D	0.68	prob.neutral	D	0.523256148	None	None	I
P/M	0.3296	likely_benign	0.3833	ambiguous	-0.312	Destabilizing	1.0	D	0.62	neutral	None	None	None	None	I
P/N	0.305	likely_benign	0.3783	ambiguous	-0.188	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
P/Q	0.1466	likely_benign	0.1761	benign	-0.443	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	I
P/R	0.1732	likely_benign	0.2227	benign	0.092	Stabilizing	0.999	D	0.675	prob.neutral	N	0.479045468	None	None	I
P/S	0.1372	likely_benign	0.1632	benign	-0.59	Destabilizing	0.995	D	0.628	neutral	N	0.490450999	None	None	I
P/T	0.1176	likely_benign	0.143	benign	-0.598	Destabilizing	0.998	D	0.634	neutral	N	0.473916906	None	None	I
P/V	0.2133	likely_benign	0.249	benign	-0.382	Destabilizing	0.998	D	0.637	neutral	None	None	None	None	I
P/W	0.7395	likely_pathogenic	0.8094	pathogenic	-0.833	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	I
P/Y	0.5133	ambiguous	0.6057	pathogenic	-0.533	Destabilizing	1.0	D	0.637	neutral	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.