TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8516	25771;25772;25773	chr2:178717188;178717187;178717186	chr2:179581915;179581914;179581913
N2AB	8199	24820;24821;24822	chr2:178717188;178717187;178717186	chr2:179581915;179581914;179581913
N2A	7272	22039;22040;22041	chr2:178717188;178717187;178717186	chr2:179581915;179581914;179581913
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: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-70
• Domain position: 61
• Structural Position: 141
• Q(SASA): 0.4082
• 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
L/F	rs775937094	-1.145	0.998	D	0.577	0.222	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	1.47E-05	0	0
L/F	rs775937094	-1.145	0.998	D	0.577	0.222	None	gnomAD-4.0.0	4.95814E-06	None	None	None	None	N	None	1.33515E-05	0	None	0	0	None	0	0	5.93391E-06	0	0
L/V	rs775937094	None	0.841	N	0.483	0.217	0.687436468124	gnomAD-4.0.0	4.1058E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49783E-06	0	1.65728E-05

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
L/A	0.3859	ambiguous	0.4437	ambiguous	-1.098	Destabilizing	0.989	D	0.493	neutral	None	None	None	None	N
L/C	0.7726	likely_pathogenic	0.7959	pathogenic	-0.856	Destabilizing	1.0	D	0.609	neutral	None	None	None	None	N
L/D	0.8509	likely_pathogenic	0.8808	pathogenic	-0.005	Destabilizing	0.997	D	0.715	prob.delet.	None	None	None	None	N
L/E	0.5277	ambiguous	0.5912	pathogenic	-0.041	Destabilizing	0.991	D	0.639	neutral	None	None	None	None	N
L/F	0.2045	likely_benign	0.2275	benign	-0.829	Destabilizing	0.998	D	0.577	neutral	D	0.533539547	None	None	N
L/G	0.6295	likely_pathogenic	0.672	pathogenic	-1.347	Destabilizing	0.998	D	0.661	neutral	None	None	None	None	N
L/H	0.3769	ambiguous	0.4066	ambiguous	-0.532	Destabilizing	0.999	D	0.69	prob.neutral	N	0.510297328	None	None	N
L/I	0.1318	likely_benign	0.1506	benign	-0.53	Destabilizing	0.924	D	0.46	neutral	N	0.516031221	None	None	N
L/K	0.4158	ambiguous	0.4503	ambiguous	-0.501	Destabilizing	0.822	D	0.579	neutral	None	None	None	None	N
L/M	0.1363	likely_benign	0.1458	benign	-0.472	Destabilizing	0.996	D	0.576	neutral	None	None	None	None	N
L/N	0.4911	ambiguous	0.5195	ambiguous	-0.312	Destabilizing	0.998	D	0.722	prob.delet.	None	None	None	None	N
L/P	0.5943	likely_pathogenic	0.6341	pathogenic	-0.686	Destabilizing	0.328	N	0.45	neutral	N	0.510932046	None	None	N
L/Q	0.173	likely_benign	0.2008	benign	-0.499	Destabilizing	0.77	D	0.405	neutral	None	None	None	None	N
L/R	0.3235	likely_benign	0.3456	ambiguous	0.004	Stabilizing	0.989	D	0.689	prob.neutral	N	0.45736692	None	None	N
L/S	0.3855	ambiguous	0.4474	ambiguous	-0.985	Destabilizing	0.997	D	0.579	neutral	None	None	None	None	N
L/T	0.3096	likely_benign	0.3649	ambiguous	-0.902	Destabilizing	0.995	D	0.546	neutral	None	None	None	None	N
L/V	0.1289	likely_benign	0.1623	benign	-0.686	Destabilizing	0.841	D	0.483	neutral	N	0.516935298	None	None	N
L/W	0.3672	ambiguous	0.3973	ambiguous	-0.814	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	N
L/Y	0.5098	ambiguous	0.5465	ambiguous	-0.567	Destabilizing	0.989	D	0.644	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.