TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20391	61396;61397;61398	chr2:178590554;178590553;178590552	chr2:179455281;179455280;179455279
N2AB	18750	56473;56474;56475	chr2:178590554;178590553;178590552	chr2:179455281;179455280;179455279
N2A	17823	53692;53693;53694	chr2:178590554;178590553;178590552	chr2:179455281;179455280;179455279
N2B	11326	34201;34202;34203	chr2:178590554;178590553;178590552	chr2:179455281;179455280;179455279
Novex-1	11451	34576;34577;34578	chr2:178590554;178590553;178590552	chr2:179455281;179455280;179455279
Novex-2	11518	34777;34778;34779	chr2:178590554;178590553;178590552	chr2:179455281;179455280;179455279
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-36
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.1975
• 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
V/E	None	None	1.0	N	0.806	0.455	0.648059144284	gnomAD-4.0.0	1.59391E-06	None	None	None	None	N	None	0	2.29211E-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
V/A	0.3693	ambiguous	0.3133	benign	-1.721	Destabilizing	0.999	D	0.567	neutral	N	0.447194707	None	None	N
V/C	0.7409	likely_pathogenic	0.699	pathogenic	-1.01	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
V/D	0.8668	likely_pathogenic	0.812	pathogenic	-2.155	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
V/E	0.6459	likely_pathogenic	0.5904	pathogenic	-2.01	Highly Destabilizing	1.0	D	0.806	deleterious	N	0.43628428	None	None	N
V/F	0.3239	likely_benign	0.2896	benign	-1.112	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
V/G	0.5124	ambiguous	0.4299	ambiguous	-2.179	Highly Destabilizing	1.0	D	0.826	deleterious	N	0.490542839	None	None	N
V/H	0.8501	likely_pathogenic	0.8005	pathogenic	-1.963	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
V/I	0.0918	likely_benign	0.0871	benign	-0.488	Destabilizing	0.998	D	0.517	neutral	None	None	None	None	N
V/K	0.8345	likely_pathogenic	0.782	pathogenic	-1.517	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
V/L	0.2947	likely_benign	0.2533	benign	-0.488	Destabilizing	0.997	D	0.555	neutral	N	0.479325768	None	None	N
V/M	0.271	likely_benign	0.229	benign	-0.3	Destabilizing	1.0	D	0.751	deleterious	N	0.509648675	None	None	N
V/N	0.6799	likely_pathogenic	0.5665	pathogenic	-1.612	Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
V/P	0.9898	likely_pathogenic	0.9881	pathogenic	-0.869	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
V/Q	0.6016	likely_pathogenic	0.5282	ambiguous	-1.572	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
V/R	0.7644	likely_pathogenic	0.7023	pathogenic	-1.211	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
V/S	0.4375	ambiguous	0.3518	ambiguous	-2.152	Highly Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
V/T	0.3193	likely_benign	0.2626	benign	-1.885	Destabilizing	0.999	D	0.631	neutral	None	None	None	None	N
V/W	0.9397	likely_pathogenic	0.9231	pathogenic	-1.622	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
V/Y	0.7441	likely_pathogenic	0.6943	pathogenic	-1.207	Destabilizing	1.0	D	0.835	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.