TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26337	79234;79235;79236	chr2:178567123;178567122;178567121	chr2:179431850;179431849;179431848
N2AB	24696	74311;74312;74313	chr2:178567123;178567122;178567121	chr2:179431850;179431849;179431848
N2A	23769	71530;71531;71532	chr2:178567123;178567122;178567121	chr2:179431850;179431849;179431848
N2B	17272	52039;52040;52041	chr2:178567123;178567122;178567121	chr2:179431850;179431849;179431848
Novex-1	17397	52414;52415;52416	chr2:178567123;178567122;178567121	chr2:179431850;179431849;179431848
Novex-2	17464	52615;52616;52617	chr2:178567123;178567122;178567121	chr2:179431850;179431849;179431848
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-79
• Domain position: 52
• Structural Position: 68
• Q(SASA): 0.3289
• 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
V/I	None	None	0.426	N	0.53	0.207	0.495839474393	gnomAD-4.0.0	1.59177E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85933E-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
V/A	0.3041	likely_benign	0.3465	ambiguous	-1.232	Destabilizing	0.426	N	0.548	neutral	N	0.476395214	None	None	I
V/C	0.8635	likely_pathogenic	0.8703	pathogenic	-1.028	Destabilizing	0.995	D	0.709	prob.delet.	None	None	None	None	I
V/D	0.9849	likely_pathogenic	0.9901	pathogenic	-1.011	Destabilizing	0.975	D	0.772	deleterious	D	0.522910073	None	None	I
V/E	0.9584	likely_pathogenic	0.967	pathogenic	-0.988	Destabilizing	0.944	D	0.686	prob.neutral	None	None	None	None	I
V/F	0.5759	likely_pathogenic	0.664	pathogenic	-0.874	Destabilizing	0.474	N	0.593	neutral	N	0.502270922	None	None	I
V/G	0.782	likely_pathogenic	0.8241	pathogenic	-1.549	Destabilizing	0.928	D	0.716	prob.delet.	D	0.523163562	None	None	I
V/H	0.9802	likely_pathogenic	0.9855	pathogenic	-0.94	Destabilizing	0.893	D	0.775	deleterious	None	None	None	None	I
V/I	0.1214	likely_benign	0.1215	benign	-0.464	Destabilizing	0.426	N	0.53	neutral	N	0.480154196	None	None	I
V/K	0.9817	likely_pathogenic	0.9873	pathogenic	-1.13	Destabilizing	0.944	D	0.694	prob.neutral	None	None	None	None	I
V/L	0.5708	likely_pathogenic	0.6458	pathogenic	-0.464	Destabilizing	0.271	N	0.455	neutral	N	0.521327106	None	None	I
V/M	0.4365	ambiguous	0.4951	ambiguous	-0.518	Destabilizing	0.981	D	0.609	neutral	None	None	None	None	I
V/N	0.9456	likely_pathogenic	0.9588	pathogenic	-1.093	Destabilizing	0.944	D	0.784	deleterious	None	None	None	None	I
V/P	0.9782	likely_pathogenic	0.9805	pathogenic	-0.685	Destabilizing	0.981	D	0.749	deleterious	None	None	None	None	I
V/Q	0.9475	likely_pathogenic	0.9578	pathogenic	-1.186	Destabilizing	0.944	D	0.753	deleterious	None	None	None	None	I
V/R	0.9705	likely_pathogenic	0.9776	pathogenic	-0.647	Destabilizing	0.944	D	0.783	deleterious	None	None	None	None	I
V/S	0.6823	likely_pathogenic	0.7414	pathogenic	-1.6	Destabilizing	0.944	D	0.685	prob.neutral	None	None	None	None	I
V/T	0.4455	ambiguous	0.4684	ambiguous	-1.452	Destabilizing	0.829	D	0.519	neutral	None	None	None	None	I
V/W	0.9902	likely_pathogenic	0.9932	pathogenic	-1.069	Destabilizing	0.985	D	0.757	deleterious	None	None	None	None	I
V/Y	0.9503	likely_pathogenic	0.9638	pathogenic	-0.751	Destabilizing	0.007	N	0.331	neutral	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.