TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20632	62119;62120;62121	chr2:178589831;178589830;178589829	chr2:179454558;179454557;179454556
N2AB	18991	57196;57197;57198	chr2:178589831;178589830;178589829	chr2:179454558;179454557;179454556
N2A	18064	54415;54416;54417	chr2:178589831;178589830;178589829	chr2:179454558;179454557;179454556
N2B	11567	34924;34925;34926	chr2:178589831;178589830;178589829	chr2:179454558;179454557;179454556
Novex-1	11692	35299;35300;35301	chr2:178589831;178589830;178589829	chr2:179454558;179454557;179454556
Novex-2	11759	35500;35501;35502	chr2:178589831;178589830;178589829	chr2:179454558;179454557;179454556
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-37
• Domain position: 64
• Structural Position: 97
• Q(SASA): 0.9653
• 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
L/H	None	None	1.0	D	0.812	0.745	0.950074274778	gnomAD-4.0.0	1.59184E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43291E-05	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
L/A	0.972	likely_pathogenic	0.9476	pathogenic	-2.591	Highly Destabilizing	0.997	D	0.789	deleterious	None	None	None	None	I
L/C	0.9695	likely_pathogenic	0.9179	pathogenic	-2.363	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
L/D	0.9987	likely_pathogenic	0.9984	pathogenic	-3.282	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
L/E	0.9955	likely_pathogenic	0.9943	pathogenic	-3.072	Highly Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
L/F	0.8247	likely_pathogenic	0.7975	pathogenic	-1.655	Destabilizing	0.999	D	0.843	deleterious	D	0.609953219	None	None	I
L/G	0.9873	likely_pathogenic	0.9767	pathogenic	-3.123	Highly Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
L/H	0.9915	likely_pathogenic	0.988	pathogenic	-2.655	Highly Destabilizing	1.0	D	0.812	deleterious	D	0.636298548	None	None	I
L/I	0.3502	ambiguous	0.3001	benign	-1.053	Destabilizing	0.992	D	0.783	deleterious	D	0.597103801	None	None	I
L/K	0.989	likely_pathogenic	0.9847	pathogenic	-2.029	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
L/M	0.4936	ambiguous	0.4508	ambiguous	-1.209	Destabilizing	0.985	D	0.739	prob.delet.	None	None	None	None	I
L/N	0.9912	likely_pathogenic	0.9876	pathogenic	-2.439	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
L/P	0.9938	likely_pathogenic	0.9893	pathogenic	-1.547	Destabilizing	1.0	D	0.823	deleterious	D	0.652317909	None	None	I
L/Q	0.9837	likely_pathogenic	0.9798	pathogenic	-2.325	Highly Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	I
L/R	0.9839	likely_pathogenic	0.9789	pathogenic	-1.724	Destabilizing	0.999	D	0.82	deleterious	D	0.652317909	None	None	I
L/S	0.9947	likely_pathogenic	0.9899	pathogenic	-3.1	Highly Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
L/T	0.9687	likely_pathogenic	0.9415	pathogenic	-2.742	Highly Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
L/V	0.5058	ambiguous	0.3925	ambiguous	-1.547	Destabilizing	0.992	D	0.772	deleterious	D	0.597911018	None	None	I
L/W	0.99	likely_pathogenic	0.9877	pathogenic	-2.079	Highly Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
L/Y	0.9862	likely_pathogenic	0.9816	pathogenic	-1.81	Destabilizing	1.0	D	0.845	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.