TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20061	60406;60407;60408	chr2:178591638;178591637;178591636	chr2:179456365;179456364;179456363
N2AB	18420	55483;55484;55485	chr2:178591638;178591637;178591636	chr2:179456365;179456364;179456363
N2A	17493	52702;52703;52704	chr2:178591638;178591637;178591636	chr2:179456365;179456364;179456363
N2B	10996	33211;33212;33213	chr2:178591638;178591637;178591636	chr2:179456365;179456364;179456363
Novex-1	11121	33586;33587;33588	chr2:178591638;178591637;178591636	chr2:179456365;179456364;179456363
Novex-2	11188	33787;33788;33789	chr2:178591638;178591637;178591636	chr2:179456365;179456364;179456363
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: Fn3-33
• Domain position: 85
• Structural Position: 120
• Q(SASA): 0.2574
• 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	1.0	N	0.777	0.482	0.745533171595	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	0.2132	likely_benign	0.226	benign	-1.637	Destabilizing	1.0	D	0.703	prob.neutral	N	0.467023464	None	None	I
P/C	0.8626	likely_pathogenic	0.8966	pathogenic	-1.023	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	I
P/D	0.9573	likely_pathogenic	0.9648	pathogenic	-1.684	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
P/E	0.8924	likely_pathogenic	0.8935	pathogenic	-1.703	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
P/F	0.903	likely_pathogenic	0.9252	pathogenic	-1.307	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
P/G	0.7953	likely_pathogenic	0.8038	pathogenic	-1.932	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	I
P/H	0.7624	likely_pathogenic	0.8059	pathogenic	-1.426	Destabilizing	1.0	D	0.77	deleterious	N	0.50525989	None	None	I
P/I	0.8971	likely_pathogenic	0.9083	pathogenic	-0.925	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
P/K	0.947	likely_pathogenic	0.9465	pathogenic	-1.417	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
P/L	0.697	likely_pathogenic	0.7	pathogenic	-0.925	Destabilizing	1.0	D	0.777	deleterious	N	0.505687509	None	None	I
P/M	0.8706	likely_pathogenic	0.8823	pathogenic	-0.658	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
P/N	0.9435	likely_pathogenic	0.9547	pathogenic	-1.164	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
P/Q	0.7919	likely_pathogenic	0.8005	pathogenic	-1.396	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	I
P/R	0.8663	likely_pathogenic	0.8651	pathogenic	-0.786	Destabilizing	1.0	D	0.779	deleterious	N	0.510829297	None	None	I
P/S	0.5136	ambiguous	0.5697	pathogenic	-1.623	Destabilizing	1.0	D	0.754	deleterious	N	0.489749301	None	None	I
P/T	0.5642	likely_pathogenic	0.5997	pathogenic	-1.548	Destabilizing	1.0	D	0.747	deleterious	N	0.511082787	None	None	I
P/V	0.762	likely_pathogenic	0.7678	pathogenic	-1.129	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
P/W	0.9071	likely_pathogenic	0.9394	pathogenic	-1.466	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	I
P/Y	0.8912	likely_pathogenic	0.9127	pathogenic	-1.221	Destabilizing	1.0	D	0.803	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.