TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15480	46663;46664;46665	chr2:178619879;178619878;178619877	chr2:179484606;179484605;179484604
N2AB	13839	41740;41741;41742	chr2:178619879;178619878;178619877	chr2:179484606;179484605;179484604
N2A	12912	38959;38960;38961	chr2:178619879;178619878;178619877	chr2:179484606;179484605;179484604
N2B	6415	19468;19469;19470	chr2:178619879;178619878;178619877	chr2:179484606;179484605;179484604
Novex-1	6540	19843;19844;19845	chr2:178619879;178619878;178619877	chr2:179484606;179484605;179484604
Novex-2	6607	20044;20045;20046	chr2:178619879;178619878;178619877	chr2:179484606;179484605;179484604
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-107
• Domain position: 1
• Structural Position: 1
• Q(SASA): 1.0718
• 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
V/L	rs777031546	-0.041	0.489	N	0.575	0.345	0.535537035517	gnomAD-2.1.1	8.29E-06	None	None	None	None	N	None	1.30736E-04	0	None	0	0	None	0	None	0	0	0
V/L	rs777031546	-0.041	0.489	N	0.575	0.345	0.535537035517	gnomAD-4.0.0	1.60893E-06	None	None	None	None	N	None	5.83567E-05	0	None	0	0	None	0	0	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
V/A	0.5821	likely_pathogenic	0.5612	ambiguous	-1.618	Destabilizing	0.489	N	0.56	neutral	D	0.549316858	None	None	N
V/C	0.9406	likely_pathogenic	0.9496	pathogenic	-0.913	Destabilizing	0.998	D	0.474	neutral	None	None	None	None	N
V/D	0.9431	likely_pathogenic	0.9531	pathogenic	-1.724	Destabilizing	0.942	D	0.561	neutral	D	0.548318616	None	None	N
V/E	0.8685	likely_pathogenic	0.8962	pathogenic	-1.711	Destabilizing	0.978	D	0.513	neutral	None	None	None	None	N
V/F	0.699	likely_pathogenic	0.7108	pathogenic	-1.244	Destabilizing	0.942	D	0.425	neutral	D	0.548636211	None	None	N
V/G	0.8101	likely_pathogenic	0.8268	pathogenic	-1.949	Destabilizing	0.014	N	0.449	neutral	D	0.548163636	None	None	N
V/H	0.9766	likely_pathogenic	0.982	pathogenic	-1.605	Destabilizing	0.998	D	0.587	neutral	None	None	None	None	N
V/I	0.1114	likely_benign	0.104	benign	-0.791	Destabilizing	0.014	N	0.395	neutral	D	0.533654946	None	None	N
V/K	0.9356	likely_pathogenic	0.9547	pathogenic	-1.509	Destabilizing	0.956	D	0.515	neutral	None	None	None	None	N
V/L	0.4693	ambiguous	0.4544	ambiguous	-0.791	Destabilizing	0.489	N	0.575	neutral	N	0.509664416	None	None	N
V/M	0.4656	ambiguous	0.4591	ambiguous	-0.531	Destabilizing	0.956	D	0.454	neutral	None	None	None	None	N
V/N	0.8901	likely_pathogenic	0.9026	pathogenic	-1.226	Destabilizing	0.956	D	0.556	neutral	None	None	None	None	N
V/P	0.7906	likely_pathogenic	0.784	pathogenic	-1.034	Destabilizing	0.993	D	0.503	neutral	None	None	None	None	N
V/Q	0.9126	likely_pathogenic	0.929	pathogenic	-1.38	Destabilizing	0.993	D	0.511	neutral	None	None	None	None	N
V/R	0.9028	likely_pathogenic	0.93	pathogenic	-0.979	Destabilizing	0.978	D	0.559	neutral	None	None	None	None	N
V/S	0.777	likely_pathogenic	0.7951	pathogenic	-1.665	Destabilizing	0.956	D	0.424	neutral	None	None	None	None	N
V/T	0.4852	ambiguous	0.5179	ambiguous	-1.549	Destabilizing	0.86	D	0.456	neutral	None	None	None	None	N
V/W	0.9832	likely_pathogenic	0.9877	pathogenic	-1.494	Destabilizing	0.998	D	0.653	neutral	None	None	None	None	N
V/Y	0.9479	likely_pathogenic	0.9567	pathogenic	-1.221	Destabilizing	0.993	D	0.437	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.