TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35720	107383;107384;107385	chr2:178528593;178528592;178528591	chr2:179393320;179393319;179393318
N2AB	34079	102460;102461;102462	chr2:178528593;178528592;178528591	chr2:179393320;179393319;179393318
N2A	33152	99679;99680;99681	chr2:178528593;178528592;178528591	chr2:179393320;179393319;179393318
N2B	26655	80188;80189;80190	chr2:178528593;178528592;178528591	chr2:179393320;179393319;179393318
Novex-1	26780	80563;80564;80565	chr2:178528593;178528592;178528591	chr2:179393320;179393319;179393318
Novex-2	26847	80764;80765;80766	chr2:178528593;178528592;178528591	chr2:179393320;179393319;179393318
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-168
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.3315
• 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/I	None	None	0.01	N	0.478	0.044	0.252681307341	gnomAD-4.0.0	6.37355E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86126E-06	4.3075E-05	0
L/P	None	None	0.295	N	0.614	0.248	0.60282686728	gnomAD-4.0.0	6.84552E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99722E-07	0	0
L/R	rs768060182	-0.618	None	N	0.517	0.204	0.411665641125	gnomAD-4.0.0	6.84552E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16144E-05	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
L/A	0.1815	likely_benign	0.1778	benign	-1.344	Destabilizing	0.016	N	0.483	neutral	None	None	None	None	N
L/C	0.4052	ambiguous	0.3905	ambiguous	-0.896	Destabilizing	0.676	D	0.547	neutral	None	None	None	None	N
L/D	0.5454	ambiguous	0.5337	ambiguous	-0.442	Destabilizing	0.072	N	0.599	neutral	None	None	None	None	N
L/E	0.3009	likely_benign	0.2887	benign	-0.436	Destabilizing	0.038	N	0.531	neutral	None	None	None	None	N
L/F	0.1133	likely_benign	0.1098	benign	-0.833	Destabilizing	0.171	N	0.541	neutral	N	0.477738539	None	None	N
L/G	0.4829	ambiguous	0.4813	ambiguous	-1.658	Destabilizing	0.072	N	0.52	neutral	None	None	None	None	N
L/H	0.122	likely_benign	0.1183	benign	-0.763	Destabilizing	None	N	0.541	neutral	N	0.472447363	None	None	N
L/I	0.0639	likely_benign	0.0612	benign	-0.57	Destabilizing	0.01	N	0.478	neutral	N	0.44599148	None	None	N
L/K	0.2167	likely_benign	0.2106	benign	-0.825	Destabilizing	None	N	0.481	neutral	None	None	None	None	N
L/M	0.1073	likely_benign	0.1094	benign	-0.541	Destabilizing	0.214	N	0.564	neutral	None	None	None	None	N
L/N	0.2565	likely_benign	0.25	benign	-0.682	Destabilizing	0.038	N	0.574	neutral	None	None	None	None	N
L/P	0.8015	likely_pathogenic	0.7864	pathogenic	-0.795	Destabilizing	0.295	N	0.614	neutral	N	0.472657507	None	None	N
L/Q	0.1124	likely_benign	0.1097	benign	-0.814	Destabilizing	0.214	N	0.605	neutral	None	None	None	None	N
L/R	0.1241	likely_benign	0.12	benign	-0.287	Destabilizing	None	N	0.517	neutral	N	0.409993395	None	None	N
L/S	0.1704	likely_benign	0.164	benign	-1.341	Destabilizing	0.038	N	0.535	neutral	None	None	None	None	N
L/T	0.1246	likely_benign	0.1202	benign	-1.209	Destabilizing	0.001	N	0.353	neutral	None	None	None	None	N
L/V	0.0682	likely_benign	0.0655	benign	-0.795	Destabilizing	None	N	0.302	neutral	N	0.410473397	None	None	N
L/W	0.2422	likely_benign	0.2433	benign	-0.873	Destabilizing	0.864	D	0.618	neutral	None	None	None	None	N
L/Y	0.2597	likely_benign	0.2588	benign	-0.648	Destabilizing	0.12	N	0.595	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.