TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14997	45214;45215;45216	chr2:178621933;178621932;178621931	chr2:179486660;179486659;179486658
N2AB	13356	40291;40292;40293	chr2:178621933;178621932;178621931	chr2:179486660;179486659;179486658
N2A	12429	37510;37511;37512	chr2:178621933;178621932;178621931	chr2:179486660;179486659;179486658
N2B	5932	18019;18020;18021	chr2:178621933;178621932;178621931	chr2:179486660;179486659;179486658
Novex-1	6057	18394;18395;18396	chr2:178621933;178621932;178621931	chr2:179486660;179486659;179486658
Novex-2	6124	18595;18596;18597	chr2:178621933;178621932;178621931	chr2:179486660;179486659;179486658
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-101
• Domain position: 56
• Structural Position: 137
• Q(SASA): 0.1037
• 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
I/V	rs1437722307	-1.601	0.4	N	0.265	0.076	0.575180444326	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
I/V	rs1437722307	-1.601	0.4	N	0.265	0.076	0.575180444326	gnomAD-4.0.0	1.59532E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43451E-05	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
I/A	0.8391	likely_pathogenic	0.7787	pathogenic	-2.924	Highly Destabilizing	0.985	D	0.642	neutral	None	None	None	None	N
I/C	0.9089	likely_pathogenic	0.8765	pathogenic	-2.04	Highly Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
I/D	0.9694	likely_pathogenic	0.9479	pathogenic	-3.562	Highly Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
I/E	0.8738	likely_pathogenic	0.8291	pathogenic	-3.305	Highly Destabilizing	0.999	D	0.768	deleterious	None	None	None	None	N
I/F	0.401	ambiguous	0.3343	benign	-1.734	Destabilizing	0.994	D	0.64	neutral	N	0.508038287	None	None	N
I/G	0.9525	likely_pathogenic	0.9296	pathogenic	-3.449	Highly Destabilizing	0.999	D	0.766	deleterious	None	None	None	None	N
I/H	0.8601	likely_pathogenic	0.8066	pathogenic	-2.993	Highly Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
I/K	0.8445	likely_pathogenic	0.7865	pathogenic	-2.338	Highly Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
I/L	0.3282	likely_benign	0.2817	benign	-1.36	Destabilizing	0.061	N	0.293	neutral	N	0.508808225	None	None	N
I/M	0.2293	likely_benign	0.2022	benign	-1.36	Destabilizing	0.994	D	0.661	neutral	N	0.508055853	None	None	N
I/N	0.7198	likely_pathogenic	0.6501	pathogenic	-2.809	Highly Destabilizing	0.999	D	0.799	deleterious	N	0.508176558	None	None	N
I/P	0.9964	likely_pathogenic	0.9926	pathogenic	-1.871	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
I/Q	0.8233	likely_pathogenic	0.7704	pathogenic	-2.603	Highly Destabilizing	0.999	D	0.798	deleterious	None	None	None	None	N
I/R	0.8034	likely_pathogenic	0.7288	pathogenic	-2.07	Highly Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
I/S	0.7171	likely_pathogenic	0.6493	pathogenic	-3.373	Highly Destabilizing	0.997	D	0.704	prob.neutral	N	0.459921882	None	None	N
I/T	0.6663	likely_pathogenic	0.5975	pathogenic	-2.99	Highly Destabilizing	0.98	D	0.689	prob.neutral	N	0.465527789	None	None	N
I/V	0.1785	likely_benign	0.1614	benign	-1.871	Destabilizing	0.4	N	0.265	neutral	N	0.485558266	None	None	N
I/W	0.9226	likely_pathogenic	0.8962	pathogenic	-2.212	Highly Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
I/Y	0.6958	likely_pathogenic	0.6421	pathogenic	-2.001	Highly Destabilizing	0.999	D	0.746	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.