TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9739	29440;29441;29442	chr2:178706659;178706658;178706657	chr2:179571386;179571385;179571384
N2AB	9422	28489;28490;28491	chr2:178706659;178706658;178706657	chr2:179571386;179571385;179571384
N2A	8495	25708;25709;25710	chr2:178706659;178706658;178706657	chr2:179571386;179571385;179571384
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: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-83
• Domain position: 42
• Structural Position: 58
• Q(SASA): 0.2319
• 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/P	None	None	0.997	None	0.781	0.688	0.857678863562	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
L/A	0.9787	likely_pathogenic	0.9406	pathogenic	-2.426	Highly Destabilizing	0.953	D	0.463	neutral	None	None	None	None	N
L/C	0.9821	likely_pathogenic	0.9454	pathogenic	-1.798	Destabilizing	0.999	D	0.642	neutral	None	None	None	None	N
L/D	0.9992	likely_pathogenic	0.9973	pathogenic	-2.03	Highly Destabilizing	0.998	D	0.777	deleterious	None	None	None	None	N
L/E	0.9937	likely_pathogenic	0.9805	pathogenic	-1.852	Destabilizing	0.998	D	0.765	deleterious	None	None	None	None	N
L/F	0.8774	likely_pathogenic	0.6379	pathogenic	-1.456	Destabilizing	0.986	D	0.571	neutral	None	None	None	None	N
L/G	0.9952	likely_pathogenic	0.9857	pathogenic	-2.928	Highly Destabilizing	0.993	D	0.747	deleterious	None	None	None	None	N
L/H	0.9893	likely_pathogenic	0.9588	pathogenic	-2.051	Highly Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
L/I	0.2557	likely_benign	0.1489	benign	-1.01	Destabilizing	0.06	N	0.338	neutral	None	None	None	None	N
L/K	0.9839	likely_pathogenic	0.9581	pathogenic	-1.881	Destabilizing	0.993	D	0.692	prob.neutral	None	None	None	None	N
L/M	0.4173	ambiguous	0.2609	benign	-0.952	Destabilizing	0.58	D	0.41	neutral	None	None	None	None	N
L/N	0.9948	likely_pathogenic	0.9822	pathogenic	-2.051	Highly Destabilizing	0.998	D	0.78	deleterious	None	None	None	None	N
L/P	0.9939	likely_pathogenic	0.9783	pathogenic	-1.459	Destabilizing	0.997	D	0.781	deleterious	None	None	None	None	N
L/Q	0.9763	likely_pathogenic	0.9224	pathogenic	-1.977	Destabilizing	0.991	D	0.73	prob.delet.	None	None	None	None	N
L/R	0.9796	likely_pathogenic	0.9435	pathogenic	-1.493	Destabilizing	0.991	D	0.719	prob.delet.	None	None	None	None	N
L/S	0.9965	likely_pathogenic	0.984	pathogenic	-2.823	Highly Destabilizing	0.993	D	0.662	neutral	None	None	None	None	N
L/T	0.9816	likely_pathogenic	0.944	pathogenic	-2.487	Highly Destabilizing	0.986	D	0.585	neutral	None	None	None	None	N
L/V	0.4618	ambiguous	0.2768	benign	-1.459	Destabilizing	0.76	D	0.475	neutral	None	None	None	None	N
L/W	0.9622	likely_pathogenic	0.8484	pathogenic	-1.626	Destabilizing	0.999	D	0.702	prob.neutral	None	None	None	None	N
L/Y	0.9812	likely_pathogenic	0.931	pathogenic	-1.399	Destabilizing	0.998	D	0.667	neutral	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.