TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16701	50326;50327;50328	chr2:178612424;178612423;178612422	chr2:179477151;179477150;179477149
N2AB	15060	45403;45404;45405	chr2:178612424;178612423;178612422	chr2:179477151;179477150;179477149
N2A	14133	42622;42623;42624	chr2:178612424;178612423;178612422	chr2:179477151;179477150;179477149
N2B	7636	23131;23132;23133	chr2:178612424;178612423;178612422	chr2:179477151;179477150;179477149
Novex-1	7761	23506;23507;23508	chr2:178612424;178612423;178612422	chr2:179477151;179477150;179477149
Novex-2	7828	23707;23708;23709	chr2:178612424;178612423;178612422	chr2:179477151;179477150;179477149
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-9
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.2819
• 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/M	None	None	1.0	D	0.715	0.37	0.566956417683	gnomAD-4.0.0	1.5939E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8622E-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
V/A	0.5336	ambiguous	0.4835	ambiguous	-1.453	Destabilizing	0.999	D	0.581	neutral	N	0.518777722	None	None	N
V/C	0.929	likely_pathogenic	0.9141	pathogenic	-1.011	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
V/D	0.9871	likely_pathogenic	0.9912	pathogenic	-1.299	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
V/E	0.9523	likely_pathogenic	0.9672	pathogenic	-1.329	Destabilizing	1.0	D	0.791	deleterious	D	0.631769518	None	None	N
V/F	0.7605	likely_pathogenic	0.8151	pathogenic	-1.265	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
V/G	0.887	likely_pathogenic	0.8911	pathogenic	-1.741	Destabilizing	1.0	D	0.791	deleterious	D	0.603607762	None	None	N
V/H	0.9859	likely_pathogenic	0.9901	pathogenic	-1.275	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
V/I	0.1252	likely_benign	0.1314	benign	-0.774	Destabilizing	0.998	D	0.502	neutral	None	None	None	None	N
V/K	0.9692	likely_pathogenic	0.9839	pathogenic	-1.211	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
V/L	0.7	likely_pathogenic	0.7372	pathogenic	-0.774	Destabilizing	0.997	D	0.56	neutral	N	0.511282992	None	None	N
V/M	0.5581	ambiguous	0.5727	pathogenic	-0.562	Destabilizing	1.0	D	0.715	prob.delet.	D	0.643104867	None	None	N
V/N	0.9384	likely_pathogenic	0.9546	pathogenic	-0.984	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
V/P	0.9829	likely_pathogenic	0.9851	pathogenic	-0.965	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
V/Q	0.9368	likely_pathogenic	0.9555	pathogenic	-1.199	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
V/R	0.9574	likely_pathogenic	0.9757	pathogenic	-0.645	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
V/S	0.7961	likely_pathogenic	0.7954	pathogenic	-1.472	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
V/T	0.5396	ambiguous	0.5224	ambiguous	-1.394	Destabilizing	0.999	D	0.612	neutral	None	None	None	None	N
V/W	0.9943	likely_pathogenic	0.9962	pathogenic	-1.414	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
V/Y	0.9738	likely_pathogenic	0.9828	pathogenic	-1.128	Destabilizing	1.0	D	0.819	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.