TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7279	22060;22061;22062	chr2:178723172;178723171;178723170	chr2:179587899;179587898;179587897
N2AB	6962	21109;21110;21111	chr2:178723172;178723171;178723170	chr2:179587899;179587898;179587897
N2A	6035	18328;18329;18330	chr2:178723172;178723171;178723170	chr2:179587899;179587898;179587897
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-57
• Domain position: 50
• Structural Position: 125
• Q(SASA): 0.4135
• Predicted PPI site: I

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/D	None	None	0.324	N	0.459	0.27	0.649841373658	gnomAD-4.0.0	1.59188E-06	None	None	None	None	I	None	5.66187E-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	0.15	likely_benign	0.1855	benign	-0.845	Destabilizing	0.09	N	0.255	neutral	N	0.481782575	None	None	I
V/C	0.694	likely_pathogenic	0.7408	pathogenic	-0.624	Destabilizing	0.981	D	0.394	neutral	None	None	None	None	I
V/D	0.2754	likely_benign	0.3623	ambiguous	-0.644	Destabilizing	0.324	N	0.459	neutral	N	0.454577331	None	None	I
V/E	0.2134	likely_benign	0.2785	benign	-0.735	Destabilizing	0.388	N	0.413	neutral	None	None	None	None	I
V/F	0.1078	likely_benign	0.1323	benign	-0.914	Destabilizing	0.627	D	0.411	neutral	N	0.485497671	None	None	I
V/G	0.222	likely_benign	0.2745	benign	-1.046	Destabilizing	0.324	N	0.447	neutral	N	0.496194667	None	None	I
V/H	0.3798	ambiguous	0.47	ambiguous	-0.614	Destabilizing	0.981	D	0.461	neutral	None	None	None	None	I
V/I	0.0688	likely_benign	0.0748	benign	-0.443	Destabilizing	0.001	N	0.123	neutral	N	0.4270468	None	None	I
V/K	0.2463	likely_benign	0.3093	benign	-0.698	Destabilizing	0.388	N	0.413	neutral	None	None	None	None	I
V/L	0.1397	likely_benign	0.167	benign	-0.443	Destabilizing	0.015	N	0.193	neutral	N	0.443688334	None	None	I
V/M	0.1085	likely_benign	0.131	benign	-0.301	Destabilizing	0.69	D	0.411	neutral	None	None	None	None	I
V/N	0.1918	likely_benign	0.2458	benign	-0.383	Destabilizing	0.69	D	0.477	neutral	None	None	None	None	I
V/P	0.8639	likely_pathogenic	0.8876	pathogenic	-0.541	Destabilizing	0.818	D	0.456	neutral	None	None	None	None	I
V/Q	0.2328	likely_benign	0.2917	benign	-0.647	Destabilizing	0.818	D	0.488	neutral	None	None	None	None	I
V/R	0.212	likely_benign	0.2626	benign	-0.129	Destabilizing	0.69	D	0.497	neutral	None	None	None	None	I
V/S	0.1558	likely_benign	0.1947	benign	-0.794	Destabilizing	0.241	N	0.399	neutral	None	None	None	None	I
V/T	0.1091	likely_benign	0.1383	benign	-0.783	Destabilizing	0.001	N	0.09	neutral	None	None	None	None	I
V/W	0.6794	likely_pathogenic	0.7561	pathogenic	-1.012	Destabilizing	0.981	D	0.495	neutral	None	None	None	None	I
V/Y	0.3882	ambiguous	0.4507	ambiguous	-0.717	Destabilizing	0.818	D	0.419	neutral	None	None	None	None	I

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.