TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9078	27457;27458;27459	chr2:178712793;178712792;178712791	chr2:179577520;179577519;179577518
N2AB	8761	26506;26507;26508	chr2:178712793;178712792;178712791	chr2:179577520;179577519;179577518
N2A	7834	23725;23726;23727	chr2:178712793;178712792;178712791	chr2:179577520;179577519;179577518
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: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-76
• Domain position: 60
• Structural Position: 140
• Q(SASA): 0.1187
• Predicted PPI site: N

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/F	None	None	0.993	N	0.799	0.43	0.476832112026	gnomAD-4.0.0	6.84223E-07	None	None	None	None	N	None	0	2.23684E-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
L/A	0.821	likely_pathogenic	0.8756	pathogenic	-2.743	Highly Destabilizing	0.983	D	0.739	prob.delet.	None	None	None	None	N
L/C	0.7582	likely_pathogenic	0.8141	pathogenic	-2.074	Highly Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
L/D	0.9845	likely_pathogenic	0.9924	pathogenic	-3.286	Highly Destabilizing	0.999	D	0.873	deleterious	None	None	None	None	N
L/E	0.9392	likely_pathogenic	0.964	pathogenic	-2.967	Highly Destabilizing	0.998	D	0.853	deleterious	None	None	None	None	N
L/F	0.2329	likely_benign	0.2803	benign	-1.632	Destabilizing	0.993	D	0.799	deleterious	N	0.504218793	None	None	N
L/G	0.9518	likely_pathogenic	0.9729	pathogenic	-3.379	Highly Destabilizing	0.998	D	0.849	deleterious	None	None	None	None	N
L/H	0.8023	likely_pathogenic	0.874	pathogenic	-2.987	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
L/I	0.0898	likely_benign	0.1001	benign	-0.847	Destabilizing	0.966	D	0.581	neutral	None	None	None	None	N
L/K	0.9007	likely_pathogenic	0.9435	pathogenic	-2.134	Highly Destabilizing	0.998	D	0.851	deleterious	None	None	None	None	N
L/M	0.1699	likely_benign	0.1783	benign	-0.97	Destabilizing	0.898	D	0.541	neutral	N	0.501243052	None	None	N
L/N	0.9285	likely_pathogenic	0.9623	pathogenic	-2.778	Highly Destabilizing	0.999	D	0.873	deleterious	None	None	None	None	N
L/P	0.9833	likely_pathogenic	0.9927	pathogenic	-1.466	Destabilizing	0.999	D	0.87	deleterious	None	None	None	None	N
L/Q	0.7971	likely_pathogenic	0.8606	pathogenic	-2.454	Highly Destabilizing	0.998	D	0.865	deleterious	None	None	None	None	N
L/R	0.8138	likely_pathogenic	0.8834	pathogenic	-2.113	Highly Destabilizing	0.998	D	0.849	deleterious	None	None	None	None	N
L/S	0.9222	likely_pathogenic	0.9576	pathogenic	-3.452	Highly Destabilizing	0.997	D	0.852	deleterious	D	0.557823996	None	None	N
L/T	0.8377	likely_pathogenic	0.8976	pathogenic	-2.958	Highly Destabilizing	0.995	D	0.809	deleterious	None	None	None	None	N
L/V	0.136	likely_benign	0.1542	benign	-1.466	Destabilizing	0.955	D	0.6	neutral	N	0.495581058	None	None	N
L/W	0.593	likely_pathogenic	0.7011	pathogenic	-2.054	Highly Destabilizing	1.0	D	0.833	deleterious	D	0.54672118	None	None	N
L/Y	0.6011	likely_pathogenic	0.7126	pathogenic	-1.786	Destabilizing	0.998	D	0.826	deleterious	None	None	None	None	N

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.