TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9727	29404;29405;29406	chr2:178706695;178706694;178706693	chr2:179571422;179571421;179571420
N2AB	9410	28453;28454;28455	chr2:178706695;178706694;178706693	chr2:179571422;179571421;179571420
N2A	8483	25672;25673;25674	chr2:178706695;178706694;178706693	chr2:179571422;179571421;179571420
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-83
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.1557
• 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	None	0.821	0.541	0.851167519305	gnomAD-4.0.0	1.369E-06	None	None	None	None	I	None	2.98989E-05	0	None	0	0	None	0	0	8.9986E-07	0	0
P/S	None	None	1.0	None	0.824	0.564	0.614155820699	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	0.9332	likely_pathogenic	0.8097	pathogenic	-1.88	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
P/C	0.9971	likely_pathogenic	0.9884	pathogenic	-1.356	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	I
P/D	0.9998	likely_pathogenic	0.9992	pathogenic	-2.281	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
P/E	0.999	likely_pathogenic	0.9966	pathogenic	-2.13	Highly Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	I
P/F	0.9997	likely_pathogenic	0.9982	pathogenic	-1.107	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	I
P/G	0.9941	likely_pathogenic	0.9848	pathogenic	-2.33	Highly Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
P/H	0.9988	likely_pathogenic	0.9948	pathogenic	-2.002	Highly Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	I
P/I	0.9974	likely_pathogenic	0.9844	pathogenic	-0.653	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
P/K	0.9991	likely_pathogenic	0.997	pathogenic	-1.363	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	I
P/L	0.989	likely_pathogenic	0.9469	pathogenic	-0.653	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
P/M	0.9992	likely_pathogenic	0.9938	pathogenic	-0.72	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
P/N	0.9996	likely_pathogenic	0.9986	pathogenic	-1.499	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
P/Q	0.998	likely_pathogenic	0.9894	pathogenic	-1.457	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
P/R	0.9964	likely_pathogenic	0.9863	pathogenic	-1.142	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	I
P/S	0.9927	likely_pathogenic	0.9722	pathogenic	-2.083	Highly Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	I
P/T	0.9919	likely_pathogenic	0.9659	pathogenic	-1.813	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
P/V	0.9914	likely_pathogenic	0.9633	pathogenic	-1.034	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
P/W	0.9998	likely_pathogenic	0.999	pathogenic	-1.534	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	I
P/Y	0.9997	likely_pathogenic	0.9985	pathogenic	-1.186	Destabilizing	1.0	D	0.809	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.