TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1870	5833;5834;5835	chr2:178776256;178776255;178776254	chr2:179640983;179640982;179640981
N2AB	1870	5833;5834;5835	chr2:178776256;178776255;178776254	chr2:179640983;179640982;179640981
N2A	1870	5833;5834;5835	chr2:178776256;178776255;178776254	chr2:179640983;179640982;179640981
N2B	1824	5695;5696;5697	chr2:178776256;178776255;178776254	chr2:179640983;179640982;179640981
Novex-1	1824	5695;5696;5697	chr2:178776256;178776255;178776254	chr2:179640983;179640982;179640981
Novex-2	1824	5695;5696;5697	chr2:178776256;178776255;178776254	chr2:179640983;179640982;179640981
Novex-3	1870	5833;5834;5835	chr2:178776256;178776255;178776254	chr2:179640983;179640982;179640981

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-9
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.1639
• 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/S	None	None	1.0	D	0.832	0.795	0.577304025972	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	0.7736	likely_pathogenic	0.8477	pathogenic	-1.704	Destabilizing	1.0	D	0.785	deleterious	D	0.650899634	None	None	I
P/C	0.9889	likely_pathogenic	0.9907	pathogenic	-1.095	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	I
P/D	0.9994	likely_pathogenic	0.9996	pathogenic	-2.266	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
P/E	0.9979	likely_pathogenic	0.9986	pathogenic	-2.268	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
P/F	0.9996	likely_pathogenic	0.9996	pathogenic	-1.411	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
P/G	0.9838	likely_pathogenic	0.9882	pathogenic	-2.015	Highly Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
P/H	0.9985	likely_pathogenic	0.9989	pathogenic	-1.669	Destabilizing	1.0	D	0.779	deleterious	D	0.809076306	None	None	I
P/I	0.988	likely_pathogenic	0.9825	pathogenic	-0.929	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	I
P/K	0.9992	likely_pathogenic	0.9994	pathogenic	-1.425	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	I
P/L	0.973	likely_pathogenic	0.9644	pathogenic	-0.929	Destabilizing	1.0	D	0.822	deleterious	D	0.717757305	None	None	I
P/M	0.9949	likely_pathogenic	0.9928	pathogenic	-0.641	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
P/N	0.9988	likely_pathogenic	0.9989	pathogenic	-1.265	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	I
P/Q	0.9963	likely_pathogenic	0.9974	pathogenic	-1.482	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
P/R	0.9975	likely_pathogenic	0.9984	pathogenic	-0.881	Destabilizing	1.0	D	0.832	deleterious	D	0.808266828	None	None	I
P/S	0.9802	likely_pathogenic	0.9872	pathogenic	-1.662	Destabilizing	1.0	D	0.832	deleterious	D	0.736413075	None	None	I
P/T	0.972	likely_pathogenic	0.9801	pathogenic	-1.573	Destabilizing	1.0	D	0.835	deleterious	D	0.706688159	None	None	I
P/V	0.9497	likely_pathogenic	0.951	pathogenic	-1.156	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
P/W	0.9999	likely_pathogenic	0.9999	pathogenic	-1.671	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
P/Y	0.9996	likely_pathogenic	0.9997	pathogenic	-1.388	Destabilizing	1.0	D	0.813	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.