TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18630	56113;56114;56115	chr2:178601016;178601015;178601014	chr2:179465743;179465742;179465741
N2AB	16989	51190;51191;51192	chr2:178601016;178601015;178601014	chr2:179465743;179465742;179465741
N2A	16062	48409;48410;48411	chr2:178601016;178601015;178601014	chr2:179465743;179465742;179465741
N2B	9565	28918;28919;28920	chr2:178601016;178601015;178601014	chr2:179465743;179465742;179465741
Novex-1	9690	29293;29294;29295	chr2:178601016;178601015;178601014	chr2:179465743;179465742;179465741
Novex-2	9757	29494;29495;29496	chr2:178601016;178601015;178601014	chr2:179465743;179465742;179465741
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-23
• Domain position: 52
• Structural Position: 64
• Q(SASA): 0.4984
• 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
A/V	None	None	0.669	N	0.285	0.199	0.366277470483	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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
A/C	0.4219	ambiguous	0.3596	ambiguous	-0.733	Destabilizing	0.998	D	0.304	neutral	None	None	None	None	N
A/D	0.1946	likely_benign	0.1705	benign	-0.759	Destabilizing	0.801	D	0.331	neutral	N	0.401155773	None	None	N
A/E	0.1806	likely_benign	0.1553	benign	-0.885	Destabilizing	0.842	D	0.284	neutral	None	None	None	None	N
A/F	0.2648	likely_benign	0.2019	benign	-0.89	Destabilizing	0.974	D	0.386	neutral	None	None	None	None	N
A/G	0.1133	likely_benign	0.1094	benign	-0.504	Destabilizing	0.454	N	0.322	neutral	N	0.420722968	None	None	N
A/H	0.3429	ambiguous	0.2775	benign	-0.529	Destabilizing	0.998	D	0.401	neutral	None	None	None	None	N
A/I	0.1949	likely_benign	0.1408	benign	-0.356	Destabilizing	0.949	D	0.291	neutral	None	None	None	None	N
A/K	0.3213	likely_benign	0.2679	benign	-0.872	Destabilizing	0.842	D	0.276	neutral	None	None	None	None	N
A/L	0.1578	likely_benign	0.1248	benign	-0.356	Destabilizing	0.728	D	0.269	neutral	None	None	None	None	N
A/M	0.198	likely_benign	0.1448	benign	-0.499	Destabilizing	0.998	D	0.316	neutral	None	None	None	None	N
A/N	0.1378	likely_benign	0.121	benign	-0.491	Destabilizing	0.949	D	0.357	neutral	None	None	None	None	N
A/P	0.182	likely_benign	0.1799	benign	-0.34	Destabilizing	0.966	D	0.302	neutral	N	0.450389727	None	None	N
A/Q	0.2438	likely_benign	0.2021	benign	-0.753	Destabilizing	0.974	D	0.309	neutral	None	None	None	None	N
A/R	0.3246	likely_benign	0.278	benign	-0.388	Destabilizing	0.949	D	0.318	neutral	None	None	None	None	N
A/S	0.077	likely_benign	0.072	benign	-0.665	Destabilizing	0.022	N	0.177	neutral	N	0.406465592	None	None	N
A/T	0.0762	likely_benign	0.0645	benign	-0.715	Destabilizing	0.022	N	0.163	neutral	N	0.384263523	None	None	N
A/V	0.1124	likely_benign	0.0886	benign	-0.34	Destabilizing	0.669	D	0.285	neutral	N	0.436479068	None	None	N
A/W	0.6068	likely_pathogenic	0.536	ambiguous	-1.067	Destabilizing	0.998	D	0.542	neutral	None	None	None	None	N
A/Y	0.3254	likely_benign	0.2773	benign	-0.723	Destabilizing	0.991	D	0.393	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.