TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13755	41488;41489;41490	chr2:178636464;178636463;178636462	chr2:179501191;179501190;179501189
N2AB	12114	36565;36566;36567	chr2:178636464;178636463;178636462	chr2:179501191;179501190;179501189
N2A	11187	33784;33785;33786	chr2:178636464;178636463;178636462	chr2:179501191;179501190;179501189
N2B	4690	14293;14294;14295	chr2:178636464;178636463;178636462	chr2:179501191;179501190;179501189
Novex-1	4815	14668;14669;14670	chr2:178636464;178636463;178636462	chr2:179501191;179501190;179501189
Novex-2	4882	14869;14870;14871	chr2:178636464;178636463;178636462	chr2:179501191;179501190;179501189
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-87
• Domain position: 72
• Structural Position: 153
• Q(SASA): 0.3998
• 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/A	None	None	0.999	D	0.703	0.595	0.47409059586	gnomAD-4.0.0	1.59234E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85992E-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
E/A	0.3198	likely_benign	0.3941	ambiguous	-0.835	Destabilizing	0.999	D	0.703	prob.neutral	D	0.55275671	None	None	N
E/C	0.9636	likely_pathogenic	0.9766	pathogenic	-0.163	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
E/D	0.2101	likely_benign	0.2355	benign	-0.796	Destabilizing	0.999	D	0.52	neutral	N	0.511380953	None	None	N
E/F	0.9012	likely_pathogenic	0.9378	pathogenic	-0.698	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
E/G	0.5378	ambiguous	0.6484	pathogenic	-1.1	Destabilizing	1.0	D	0.756	deleterious	D	0.689128877	None	None	N
E/H	0.7862	likely_pathogenic	0.8608	pathogenic	-0.834	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
E/I	0.4445	ambiguous	0.5446	ambiguous	-0.141	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
E/K	0.3725	ambiguous	0.5241	ambiguous	-0.058	Destabilizing	0.999	D	0.607	neutral	N	0.507483618	None	None	N
E/L	0.6085	likely_pathogenic	0.7143	pathogenic	-0.141	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/M	0.6268	likely_pathogenic	0.7212	pathogenic	0.301	Stabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/N	0.3677	ambiguous	0.464	ambiguous	-0.423	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
E/P	0.8972	likely_pathogenic	0.9132	pathogenic	-0.353	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/Q	0.2939	likely_benign	0.3818	ambiguous	-0.393	Destabilizing	1.0	D	0.623	neutral	N	0.511726249	None	None	N
E/R	0.5997	likely_pathogenic	0.727	pathogenic	0.066	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
E/S	0.3685	ambiguous	0.4554	ambiguous	-0.649	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	N
E/T	0.3027	likely_benign	0.3926	ambiguous	-0.429	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/V	0.2988	likely_benign	0.3801	ambiguous	-0.353	Destabilizing	1.0	D	0.785	deleterious	N	0.496397841	None	None	N
E/W	0.9761	likely_pathogenic	0.9858	pathogenic	-0.487	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
E/Y	0.8669	likely_pathogenic	0.9172	pathogenic	-0.433	Destabilizing	1.0	D	0.793	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.