TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3892	11899;11900;11901	chr2:178741559;178741558;178741557	chr2:179606286;179606285;179606284
N2AB	3575	10948;10949;10950	chr2:178741559;178741558;178741557	chr2:179606286;179606285;179606284
N2A	None	None	chr2:None	chr2:None
N2B	3529	10810;10811;10812	chr2:178741559;178741558;178741557	chr2:179606286;179606285;179606284
Novex-1	3654	11185;11186;11187	chr2:178741559;178741558;178741557	chr2:179606286;179606285;179606284
Novex-2	3721	11386;11387;11388	chr2:178741559;178741558;178741557	chr2:179606286;179606285;179606284
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-27
• Domain position: 73
• Structural Position: 156
• Q(SASA): 0.071
• 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
C/S	None	None	1.0	D	0.835	0.708	None	gnomAD-4.0.0	1.59118E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85806E-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
C/A	0.7666	likely_pathogenic	0.7941	pathogenic	-1.558	Destabilizing	0.998	D	0.743	deleterious	None	None	None	None	N
C/D	0.9977	likely_pathogenic	0.9984	pathogenic	-1.485	Destabilizing	1.0	D	0.914	deleterious	None	None	None	None	N
C/E	0.9986	likely_pathogenic	0.9989	pathogenic	-1.231	Destabilizing	1.0	D	0.931	deleterious	None	None	None	None	N
C/F	0.6889	likely_pathogenic	0.6997	pathogenic	-0.902	Destabilizing	1.0	D	0.917	deleterious	D	0.781319746	None	None	N
C/G	0.661	likely_pathogenic	0.7058	pathogenic	-1.939	Destabilizing	1.0	D	0.908	deleterious	D	0.783992476	None	None	N
C/H	0.9915	likely_pathogenic	0.9927	pathogenic	-2.14	Highly Destabilizing	1.0	D	0.923	deleterious	None	None	None	None	N
C/I	0.8171	likely_pathogenic	0.7945	pathogenic	-0.52	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
C/K	0.9987	likely_pathogenic	0.999	pathogenic	-1.02	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
C/L	0.753	likely_pathogenic	0.7497	pathogenic	-0.52	Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
C/M	0.936	likely_pathogenic	0.9311	pathogenic	0.332	Stabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
C/N	0.991	likely_pathogenic	0.9923	pathogenic	-1.729	Destabilizing	1.0	D	0.93	deleterious	None	None	None	None	N
C/P	0.9972	likely_pathogenic	0.9974	pathogenic	-0.844	Destabilizing	1.0	D	0.929	deleterious	None	None	None	None	N
C/Q	0.9953	likely_pathogenic	0.9963	pathogenic	-1.204	Destabilizing	1.0	D	0.936	deleterious	None	None	None	None	N
C/R	0.9816	likely_pathogenic	0.9875	pathogenic	-1.494	Destabilizing	1.0	D	0.935	deleterious	D	0.783992476	None	None	N
C/S	0.8622	likely_pathogenic	0.8819	pathogenic	-2.013	Highly Destabilizing	1.0	D	0.835	deleterious	D	0.750512016	None	None	N
C/T	0.9296	likely_pathogenic	0.9306	pathogenic	-1.563	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
C/V	0.6863	likely_pathogenic	0.6679	pathogenic	-0.844	Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	N
C/W	0.9702	likely_pathogenic	0.9747	pathogenic	-1.319	Destabilizing	1.0	D	0.901	deleterious	D	0.783992476	None	None	N
C/Y	0.9161	likely_pathogenic	0.9235	pathogenic	-1.106	Destabilizing	1.0	D	0.929	deleterious	D	0.783992476	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.