TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33358	100297;100298;100299	chr2:178537037;178537036;178537035	chr2:179401764;179401763;179401762
N2AB	31717	95374;95375;95376	chr2:178537037;178537036;178537035	chr2:179401764;179401763;179401762
N2A	30790	92593;92594;92595	chr2:178537037;178537036;178537035	chr2:179401764;179401763;179401762
N2B	24293	73102;73103;73104	chr2:178537037;178537036;178537035	chr2:179401764;179401763;179401762
Novex-1	24418	73477;73478;73479	chr2:178537037;178537036;178537035	chr2:179401764;179401763;179401762
Novex-2	24485	73678;73679;73680	chr2:178537037;178537036;178537035	chr2:179401764;179401763;179401762
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: Fn3-130
• Domain position: 69
• Structural Position: 99
• Q(SASA): 0.3578
• 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	N	0.66	0.517	0.368743488249	gnomAD-4.0.0	1.36894E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79929E-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	0.3618	ambiguous	0.386	ambiguous	-0.448	Destabilizing	0.999	D	0.66	neutral	N	0.501586552	None	None	N
E/C	0.9758	likely_pathogenic	0.9794	pathogenic	-0.01	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
E/D	0.3572	ambiguous	0.3296	benign	-0.592	Destabilizing	0.999	D	0.539	neutral	N	0.468864024	None	None	N
E/F	0.9787	likely_pathogenic	0.9809	pathogenic	-0.442	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
E/G	0.4222	ambiguous	0.4119	ambiguous	-0.687	Destabilizing	1.0	D	0.657	neutral	N	0.493475965	None	None	N
E/H	0.9053	likely_pathogenic	0.9178	pathogenic	-0.562	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	N
E/I	0.8167	likely_pathogenic	0.8387	pathogenic	0.159	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
E/K	0.4231	ambiguous	0.4647	ambiguous	0.004	Stabilizing	0.999	D	0.667	neutral	N	0.493892575	None	None	N
E/L	0.8473	likely_pathogenic	0.8639	pathogenic	0.159	Stabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
E/M	0.8706	likely_pathogenic	0.8782	pathogenic	0.443	Stabilizing	1.0	D	0.653	neutral	None	None	None	None	N
E/N	0.6503	likely_pathogenic	0.6502	pathogenic	-0.187	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
E/P	0.6368	likely_pathogenic	0.7145	pathogenic	-0.022	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
E/Q	0.3723	ambiguous	0.3966	ambiguous	-0.159	Destabilizing	1.0	D	0.669	neutral	N	0.470407733	None	None	N
E/R	0.6482	likely_pathogenic	0.7058	pathogenic	0.125	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
E/S	0.5201	ambiguous	0.5177	ambiguous	-0.401	Destabilizing	0.999	D	0.696	prob.neutral	None	None	None	None	N
E/T	0.6211	likely_pathogenic	0.6492	pathogenic	-0.219	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
E/V	0.6086	likely_pathogenic	0.6455	pathogenic	-0.022	Destabilizing	1.0	D	0.67	neutral	N	0.480220329	None	None	N
E/W	0.9926	likely_pathogenic	0.9936	pathogenic	-0.349	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
E/Y	0.9559	likely_pathogenic	0.9605	pathogenic	-0.222	Destabilizing	1.0	D	0.675	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.