TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9214	27865;27866;27867	chr2:178712190;178712189;178712188	chr2:179576917;179576916;179576915
N2AB	8897	26914;26915;26916	chr2:178712190;178712189;178712188	chr2:179576917;179576916;179576915
N2A	7970	24133;24134;24135	chr2:178712190;178712189;178712188	chr2:179576917;179576916;179576915
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: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-78
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.5207
• 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/I	rs987421243	-0.025	0.489	N	0.419	0.114	0.319686207203	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	1.14837E-04	0	None	0	0	None	0	None	0	0	0
V/I	rs987421243	-0.025	0.489	N	0.419	0.114	0.319686207203	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/I	rs987421243	-0.025	0.489	N	0.419	0.114	0.319686207203	gnomAD-4.0.0	6.57462E-06	None	None	None	None	I	None	2.41266E-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	0.1564	likely_benign	0.1932	benign	-1.075	Destabilizing	0.822	D	0.374	neutral	N	0.513033776	None	None	I
V/C	0.7312	likely_pathogenic	0.781	pathogenic	-0.677	Destabilizing	0.998	D	0.373	neutral	None	None	None	None	I
V/D	0.4598	ambiguous	0.4972	ambiguous	-0.856	Destabilizing	0.99	D	0.517	neutral	N	0.518518522	None	None	I
V/E	0.2613	likely_benign	0.2757	benign	-0.889	Destabilizing	0.978	D	0.443	neutral	None	None	None	None	I
V/F	0.1683	likely_benign	0.1813	benign	-0.882	Destabilizing	0.942	D	0.329	neutral	N	0.496108626	None	None	I
V/G	0.2446	likely_benign	0.2855	benign	-1.347	Destabilizing	0.97	D	0.488	neutral	N	0.503932986	None	None	I
V/H	0.5638	ambiguous	0.5932	pathogenic	-0.985	Destabilizing	0.998	D	0.545	neutral	None	None	None	None	I
V/I	0.0737	likely_benign	0.0771	benign	-0.452	Destabilizing	0.489	N	0.419	neutral	N	0.488098046	None	None	I
V/K	0.287	likely_benign	0.2988	benign	-0.991	Destabilizing	0.978	D	0.401	neutral	None	None	None	None	I
V/L	0.1334	likely_benign	0.1452	benign	-0.452	Destabilizing	0.014	N	0.163	neutral	N	0.456236343	None	None	I
V/M	0.099	likely_benign	0.1083	benign	-0.359	Destabilizing	0.356	N	0.211	neutral	None	None	None	None	I
V/N	0.3391	likely_benign	0.3904	ambiguous	-0.697	Destabilizing	0.993	D	0.529	neutral	None	None	None	None	I
V/P	0.8464	likely_pathogenic	0.8845	pathogenic	-0.624	Destabilizing	0.993	D	0.437	neutral	None	None	None	None	I
V/Q	0.2449	likely_benign	0.2608	benign	-0.87	Destabilizing	0.978	D	0.44	neutral	None	None	None	None	I
V/R	0.2679	likely_benign	0.2808	benign	-0.508	Destabilizing	0.978	D	0.518	neutral	None	None	None	None	I
V/S	0.234	likely_benign	0.2889	benign	-1.139	Destabilizing	0.978	D	0.375	neutral	None	None	None	None	I
V/T	0.169	likely_benign	0.1965	benign	-1.066	Destabilizing	0.86	D	0.31	neutral	None	None	None	None	I
V/W	0.7774	likely_pathogenic	0.7955	pathogenic	-1.07	Destabilizing	0.998	D	0.595	neutral	None	None	None	None	I
V/Y	0.5477	ambiguous	0.5926	pathogenic	-0.771	Destabilizing	0.978	D	0.323	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.