TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13912	41959;41960;41961	chr2:178635590;178635589;178635588	chr2:179500317;179500316;179500315
N2AB	12271	37036;37037;37038	chr2:178635590;178635589;178635588	chr2:179500317;179500316;179500315
N2A	11344	34255;34256;34257	chr2:178635590;178635589;178635588	chr2:179500317;179500316;179500315
N2B	4847	14764;14765;14766	chr2:178635590;178635589;178635588	chr2:179500317;179500316;179500315
Novex-1	4972	15139;15140;15141	chr2:178635590;178635589;178635588	chr2:179500317;179500316;179500315
Novex-2	5039	15340;15341;15342	chr2:178635590;178635589;178635588	chr2:179500317;179500316;179500315
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-89
• Domain position: 37
• Structural Position: 56
• Q(SASA): 0.3759
• 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/D	rs779199526	-0.78	0.709	D	0.473	0.124	0.219573609325	gnomAD-2.1.1	4.59E-06	None	None	None	None	N	None	0	3.25E-05	None	0	0	None	0	None	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	0.3584	ambiguous	0.3364	benign	-0.735	Destabilizing	0.016	N	0.403	neutral	D	0.534190317	None	None	N
E/C	0.9701	likely_pathogenic	0.9673	pathogenic	-0.478	Destabilizing	0.992	D	0.719	prob.delet.	None	None	None	None	N
E/D	0.5049	ambiguous	0.5535	ambiguous	-0.854	Destabilizing	0.709	D	0.473	neutral	D	0.538326296	None	None	N
E/F	0.9634	likely_pathogenic	0.9669	pathogenic	-0.069	Destabilizing	0.848	D	0.723	deleterious	None	None	None	None	N
E/G	0.659	likely_pathogenic	0.6648	pathogenic	-1.068	Destabilizing	0.546	D	0.501	neutral	D	0.539661471	None	None	N
E/H	0.9262	likely_pathogenic	0.9278	pathogenic	-0.038	Destabilizing	0.992	D	0.473	neutral	None	None	None	None	N
E/I	0.634	likely_pathogenic	0.6233	pathogenic	0.164	Stabilizing	0.491	N	0.585	neutral	None	None	None	None	N
E/K	0.5681	likely_pathogenic	0.5553	ambiguous	-0.358	Destabilizing	0.709	D	0.425	neutral	N	0.446796766	None	None	N
E/L	0.7716	likely_pathogenic	0.7451	pathogenic	0.164	Stabilizing	0.444	N	0.534	neutral	None	None	None	None	N
E/M	0.764	likely_pathogenic	0.7486	pathogenic	0.358	Stabilizing	0.955	D	0.625	neutral	None	None	None	None	N
E/N	0.7471	likely_pathogenic	0.7452	pathogenic	-0.953	Destabilizing	0.972	D	0.464	neutral	None	None	None	None	N
E/P	0.7484	likely_pathogenic	0.7082	pathogenic	-0.115	Destabilizing	0.919	D	0.505	neutral	None	None	None	None	N
E/Q	0.4411	ambiguous	0.4178	ambiguous	-0.82	Destabilizing	0.963	D	0.485	neutral	N	0.495384187	None	None	N
E/R	0.7697	likely_pathogenic	0.7611	pathogenic	0.048	Stabilizing	0.919	D	0.457	neutral	None	None	None	None	N
E/S	0.5867	likely_pathogenic	0.5955	pathogenic	-1.179	Destabilizing	0.444	N	0.391	neutral	None	None	None	None	N
E/T	0.5677	likely_pathogenic	0.5579	ambiguous	-0.899	Destabilizing	0.615	D	0.509	neutral	None	None	None	None	N
E/V	0.4588	ambiguous	0.4412	ambiguous	-0.115	Destabilizing	0.004	N	0.44	neutral	N	0.492128283	None	None	N
E/W	0.9933	likely_pathogenic	0.9945	pathogenic	0.233	Stabilizing	0.992	D	0.691	prob.delet.	None	None	None	None	N
E/Y	0.9527	likely_pathogenic	0.9583	pathogenic	0.197	Stabilizing	0.919	D	0.657	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.