TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34153	102682;102683;102684	chr2:178534158;178534157;178534156	chr2:179398885;179398884;179398883
N2AB	32512	97759;97760;97761	chr2:178534158;178534157;178534156	chr2:179398885;179398884;179398883
N2A	31585	94978;94979;94980	chr2:178534158;178534157;178534156	chr2:179398885;179398884;179398883
N2B	25088	75487;75488;75489	chr2:178534158;178534157;178534156	chr2:179398885;179398884;179398883
Novex-1	25213	75862;75863;75864	chr2:178534158;178534157;178534156	chr2:179398885;179398884;179398883
Novex-2	25280	76063;76064;76065	chr2:178534158;178534157;178534156	chr2:179398885;179398884;179398883
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-160
• Domain position: 17
• Structural Position: 28
• Q(SASA): 0.1288
• 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	rs1236074112	-0.344	0.004	N	0.269	0.137	0.346085882481	gnomAD-2.1.1	8.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	8.88E-06	0
V/I	rs1236074112	-0.344	0.004	N	0.269	0.137	0.346085882481	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	2.06868E-04	0
V/I	rs1236074112	-0.344	0.004	N	0.269	0.137	0.346085882481	gnomAD-4.0.0	5.1235E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.67982E-05	5.68731E-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
V/A	0.2437	likely_benign	0.2222	benign	-1.501	Destabilizing	None	N	0.276	neutral	N	0.467734976	None	None	I
V/C	0.817	likely_pathogenic	0.8244	pathogenic	-0.782	Destabilizing	0.909	D	0.779	deleterious	None	None	None	None	I
V/D	0.9184	likely_pathogenic	0.9062	pathogenic	-1.633	Destabilizing	0.497	N	0.847	deleterious	N	0.494896954	None	None	I
V/E	0.801	likely_pathogenic	0.7727	pathogenic	-1.432	Destabilizing	0.567	D	0.806	deleterious	None	None	None	None	I
V/F	0.4796	ambiguous	0.4651	ambiguous	-0.815	Destabilizing	0.667	D	0.833	deleterious	N	0.482019711	None	None	I
V/G	0.5347	ambiguous	0.4824	ambiguous	-2.003	Highly Destabilizing	0.124	N	0.775	deleterious	N	0.467891929	None	None	I
V/H	0.9199	likely_pathogenic	0.9125	pathogenic	-1.654	Destabilizing	0.968	D	0.819	deleterious	None	None	None	None	I
V/I	0.1106	likely_benign	0.1158	benign	-0.127	Destabilizing	0.004	N	0.269	neutral	N	0.50494657	None	None	I
V/K	0.7934	likely_pathogenic	0.7585	pathogenic	-1.113	Destabilizing	0.567	D	0.802	deleterious	None	None	None	None	I
V/L	0.4146	ambiguous	0.4041	ambiguous	-0.127	Destabilizing	0.055	N	0.501	neutral	N	0.501674192	None	None	I
V/M	0.3275	likely_benign	0.3149	benign	-0.086	Destabilizing	0.726	D	0.671	neutral	None	None	None	None	I
V/N	0.807	likely_pathogenic	0.789	pathogenic	-1.357	Destabilizing	0.726	D	0.845	deleterious	None	None	None	None	I
V/P	0.9767	likely_pathogenic	0.9656	pathogenic	-0.556	Destabilizing	0.567	D	0.819	deleterious	None	None	None	None	I
V/Q	0.7539	likely_pathogenic	0.716	pathogenic	-1.208	Destabilizing	0.726	D	0.799	deleterious	None	None	None	None	I
V/R	0.7225	likely_pathogenic	0.6609	pathogenic	-1.016	Destabilizing	0.567	D	0.844	deleterious	None	None	None	None	I
V/S	0.4878	ambiguous	0.4651	ambiguous	-1.985	Destabilizing	0.157	N	0.747	deleterious	None	None	None	None	I
V/T	0.3318	likely_benign	0.3248	benign	-1.638	Destabilizing	0.157	N	0.663	neutral	None	None	None	None	I
V/W	0.9708	likely_pathogenic	0.9675	pathogenic	-1.288	Destabilizing	0.968	D	0.812	deleterious	None	None	None	None	I
V/Y	0.8686	likely_pathogenic	0.858	pathogenic	-0.827	Destabilizing	0.726	D	0.803	deleterious	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.