TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17702	53329;53330;53331	chr2:178607584;178607583;178607582	chr2:179472311;179472310;179472309
N2AB	16061	48406;48407;48408	chr2:178607584;178607583;178607582	chr2:179472311;179472310;179472309
N2A	15134	45625;45626;45627	chr2:178607584;178607583;178607582	chr2:179472311;179472310;179472309
N2B	8637	26134;26135;26136	chr2:178607584;178607583;178607582	chr2:179472311;179472310;179472309
Novex-1	8762	26509;26510;26511	chr2:178607584;178607583;178607582	chr2:179472311;179472310;179472309
Novex-2	8829	26710;26711;26712	chr2:178607584;178607583;178607582	chr2:179472311;179472310;179472309
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: Ig-113
• Domain position: 26
• Structural Position: 44
• Q(SASA): 0.1727
• 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	rs1238325853	-1.205	1.0	D	0.815	0.667	0.589813230912	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
P/S	rs1238325853	-1.205	1.0	D	0.815	0.667	0.589813230912	gnomAD-4.0.0	1.59243E-06	None	None	None	None	I	None	0	2.28686E-05	None	0	0	None	0	0	0	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	0.7819	likely_pathogenic	0.8182	pathogenic	-1.215	Destabilizing	1.0	D	0.775	deleterious	D	0.54163966	None	None	I
P/C	0.9806	likely_pathogenic	0.9831	pathogenic	-0.83	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
P/D	0.9984	likely_pathogenic	0.9989	pathogenic	-1.134	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
P/E	0.9949	likely_pathogenic	0.9964	pathogenic	-1.217	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
P/F	0.9984	likely_pathogenic	0.999	pathogenic	-1.347	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
P/G	0.9811	likely_pathogenic	0.987	pathogenic	-1.425	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
P/H	0.9941	likely_pathogenic	0.9964	pathogenic	-1.013	Destabilizing	1.0	D	0.767	deleterious	D	0.563733615	None	None	I
P/I	0.9813	likely_pathogenic	0.9849	pathogenic	-0.775	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
P/K	0.997	likely_pathogenic	0.9981	pathogenic	-0.87	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
P/L	0.9495	likely_pathogenic	0.9593	pathogenic	-0.775	Destabilizing	1.0	D	0.81	deleterious	D	0.558663824	None	None	I
P/M	0.9904	likely_pathogenic	0.9933	pathogenic	-0.462	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
P/N	0.9978	likely_pathogenic	0.9985	pathogenic	-0.598	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
P/Q	0.9889	likely_pathogenic	0.9923	pathogenic	-0.907	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
P/R	0.9894	likely_pathogenic	0.9924	pathogenic	-0.295	Destabilizing	1.0	D	0.826	deleterious	D	0.574747525	None	None	I
P/S	0.974	likely_pathogenic	0.9809	pathogenic	-1.022	Destabilizing	1.0	D	0.815	deleterious	D	0.5477425	None	None	I
P/T	0.9648	likely_pathogenic	0.9755	pathogenic	-1.01	Destabilizing	1.0	D	0.818	deleterious	D	0.562719657	None	None	I
P/V	0.9543	likely_pathogenic	0.9622	pathogenic	-0.888	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
P/W	0.9992	likely_pathogenic	0.9995	pathogenic	-1.429	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	I
P/Y	0.9985	likely_pathogenic	0.9991	pathogenic	-1.128	Destabilizing	1.0	D	0.797	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.