TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33043	99352;99353;99354	chr2:178538702;178538701;178538700	chr2:179403429;179403428;179403427
N2AB	31402	94429;94430;94431	chr2:178538702;178538701;178538700	chr2:179403429;179403428;179403427
N2A	30475	91648;91649;91650	chr2:178538702;178538701;178538700	chr2:179403429;179403428;179403427
N2B	23978	72157;72158;72159	chr2:178538702;178538701;178538700	chr2:179403429;179403428;179403427
Novex-1	24103	72532;72533;72534	chr2:178538702;178538701;178538700	chr2:179403429;179403428;179403427
Novex-2	24170	72733;72734;72735	chr2:178538702;178538701;178538700	chr2:179403429;179403428;179403427
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-129
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.9491
• 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
S/G	None	None	0.896	N	0.638	0.135	0.200317383148	gnomAD-4.0.0	2.73688E-06	None	None	None	None	N	None	0	4.47227E-05	None	0	0	None	0	0	1.79899E-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
S/A	0.0722	likely_benign	0.073	benign	-0.179	Destabilizing	0.132	N	0.32	neutral	None	None	None	None	N
S/C	0.1348	likely_benign	0.1492	benign	-0.369	Destabilizing	0.999	D	0.694	prob.neutral	N	0.500869025	None	None	N
S/D	0.617	likely_pathogenic	0.5294	ambiguous	-0.017	Destabilizing	0.919	D	0.621	neutral	None	None	None	None	N
S/E	0.7241	likely_pathogenic	0.6601	pathogenic	-0.122	Destabilizing	0.919	D	0.625	neutral	None	None	None	None	N
S/F	0.2178	likely_benign	0.2234	benign	-0.925	Destabilizing	0.988	D	0.68	prob.neutral	None	None	None	None	N
S/G	0.0911	likely_benign	0.0917	benign	-0.225	Destabilizing	0.896	D	0.638	neutral	N	0.456851553	None	None	N
S/H	0.4659	ambiguous	0.4508	ambiguous	-0.497	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
S/I	0.1517	likely_benign	0.1536	benign	-0.189	Destabilizing	0.968	D	0.66	neutral	N	0.509515389	None	None	N
S/K	0.7973	likely_pathogenic	0.7573	pathogenic	-0.387	Destabilizing	0.919	D	0.623	neutral	None	None	None	None	N
S/L	0.0904	likely_benign	0.0907	benign	-0.189	Destabilizing	0.851	D	0.591	neutral	None	None	None	None	N
S/M	0.1632	likely_benign	0.1704	benign	-0.204	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
S/N	0.144	likely_benign	0.1333	benign	-0.113	Destabilizing	0.896	D	0.623	neutral	N	0.444405118	None	None	N
S/P	0.1735	likely_benign	0.1686	benign	-0.162	Destabilizing	0.988	D	0.693	prob.neutral	None	None	None	None	N
S/Q	0.603	likely_pathogenic	0.5912	pathogenic	-0.339	Destabilizing	0.988	D	0.654	neutral	None	None	None	None	N
S/R	0.7727	likely_pathogenic	0.7392	pathogenic	-0.099	Destabilizing	0.968	D	0.687	prob.neutral	N	0.489852193	None	None	N
S/T	0.0635	likely_benign	0.0657	benign	-0.227	Destabilizing	0.103	N	0.407	neutral	N	0.46385767	None	None	N
S/V	0.1481	likely_benign	0.1536	benign	-0.162	Destabilizing	0.851	D	0.584	neutral	None	None	None	None	N
S/W	0.4934	ambiguous	0.5215	ambiguous	-1.016	Destabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	N
S/Y	0.2572	likely_benign	0.2582	benign	-0.695	Destabilizing	0.996	D	0.68	prob.neutral	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.