TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13698	41317;41318;41319	chr2:178636635;178636634;178636633	chr2:179501362;179501361;179501360
N2AB	12057	36394;36395;36396	chr2:178636635;178636634;178636633	chr2:179501362;179501361;179501360
N2A	11130	33613;33614;33615	chr2:178636635;178636634;178636633	chr2:179501362;179501361;179501360
N2B	4633	14122;14123;14124	chr2:178636635;178636634;178636633	chr2:179501362;179501361;179501360
Novex-1	4758	14497;14498;14499	chr2:178636635;178636634;178636633	chr2:179501362;179501361;179501360
Novex-2	4825	14698;14699;14700	chr2:178636635;178636634;178636633	chr2:179501362;179501361;179501360
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-87
• Domain position: 15
• Structural Position: 21
• Q(SASA): 0.2867
• 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
E/Q	rs1216328116	-0.455	1.0	N	0.605	0.231	0.414670632993	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.61E-05	None	0	None	0	0	0
E/Q	rs1216328116	-0.455	1.0	N	0.605	0.231	0.414670632993	gnomAD-4.0.0	1.59219E-06	None	None	None	None	N	None	0	0	None	0	2.78133E-05	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
E/A	0.4962	ambiguous	0.4321	ambiguous	-0.695	Destabilizing	0.999	D	0.631	neutral	N	0.444161385	None	None	N
E/C	0.9824	likely_pathogenic	0.9783	pathogenic	-0.107	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
E/D	0.2567	likely_benign	0.1983	benign	-0.374	Destabilizing	0.999	D	0.506	neutral	N	0.502575064	None	None	N
E/F	0.9782	likely_pathogenic	0.9731	pathogenic	-0.481	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
E/G	0.4935	ambiguous	0.426	ambiguous	-0.904	Destabilizing	1.0	D	0.681	prob.neutral	N	0.510570465	None	None	N
E/H	0.8776	likely_pathogenic	0.849	pathogenic	-0.313	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
E/I	0.8988	likely_pathogenic	0.8744	pathogenic	-0.168	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
E/K	0.6436	likely_pathogenic	0.5586	ambiguous	0.296	Stabilizing	0.999	D	0.613	neutral	N	0.497594499	None	None	N
E/L	0.8943	likely_pathogenic	0.8723	pathogenic	-0.168	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
E/M	0.9104	likely_pathogenic	0.8868	pathogenic	0.07	Stabilizing	1.0	D	0.662	neutral	None	None	None	None	N
E/N	0.603	likely_pathogenic	0.5431	ambiguous	-0.176	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
E/P	0.8834	likely_pathogenic	0.8466	pathogenic	-0.325	Destabilizing	1.0	D	0.662	neutral	None	None	None	None	N
E/Q	0.4189	ambiguous	0.392	ambiguous	-0.122	Destabilizing	1.0	D	0.605	neutral	N	0.492368927	None	None	N
E/R	0.7378	likely_pathogenic	0.6972	pathogenic	0.461	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
E/S	0.4694	ambiguous	0.4147	ambiguous	-0.314	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	N
E/T	0.6403	likely_pathogenic	0.5722	pathogenic	-0.13	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
E/V	0.7646	likely_pathogenic	0.7036	pathogenic	-0.325	Destabilizing	1.0	D	0.701	prob.neutral	N	0.444797087	None	None	N
E/W	0.9931	likely_pathogenic	0.993	pathogenic	-0.249	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
E/Y	0.9488	likely_pathogenic	0.9463	pathogenic	-0.223	Destabilizing	1.0	D	0.695	prob.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.