TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20785	62578;62579;62580	chr2:178589372;178589371;178589370	chr2:179454099;179454098;179454097
N2AB	19144	57655;57656;57657	chr2:178589372;178589371;178589370	chr2:179454099;179454098;179454097
N2A	18217	54874;54875;54876	chr2:178589372;178589371;178589370	chr2:179454099;179454098;179454097
N2B	11720	35383;35384;35385	chr2:178589372;178589371;178589370	chr2:179454099;179454098;179454097
Novex-1	11845	35758;35759;35760	chr2:178589372;178589371;178589370	chr2:179454099;179454098;179454097
Novex-2	11912	35959;35960;35961	chr2:178589372;178589371;178589370	chr2:179454099;179454098;179454097
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-122
• Domain position: 17
• Structural Position: 25
• Q(SASA): 0.3335
• 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
D/E	rs766020138	-0.531	0.001	N	0.157	0.069	0.0138822411134	gnomAD-2.1.1	8.06E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
D/E	rs766020138	-0.531	0.001	N	0.157	0.069	0.0138822411134	gnomAD-4.0.0	2.73738E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.59826E-06	0	0
D/Y	None	None	0.957	N	0.573	0.345	0.446310458034	gnomAD-4.0.0	6.8434E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99557E-07	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
D/A	0.3344	likely_benign	0.3698	ambiguous	-0.355	Destabilizing	0.338	N	0.403	neutral	N	0.437028067	None	None	I
D/C	0.8334	likely_pathogenic	0.8619	pathogenic	0.131	Stabilizing	0.991	D	0.658	neutral	None	None	None	None	I
D/E	0.1445	likely_benign	0.142	benign	-0.372	Destabilizing	0.001	N	0.157	neutral	N	0.392906357	None	None	I
D/F	0.8721	likely_pathogenic	0.8937	pathogenic	-0.351	Destabilizing	0.967	D	0.575	neutral	None	None	None	None	I
D/G	0.3707	ambiguous	0.4211	ambiguous	-0.567	Destabilizing	0.505	D	0.334	neutral	N	0.428445869	None	None	I
D/H	0.5958	likely_pathogenic	0.6739	pathogenic	-0.378	Destabilizing	0.879	D	0.403	neutral	N	0.461790439	None	None	I
D/I	0.7375	likely_pathogenic	0.779	pathogenic	0.158	Stabilizing	0.906	D	0.577	neutral	None	None	None	None	I
D/K	0.6433	likely_pathogenic	0.7022	pathogenic	0.329	Stabilizing	0.018	N	0.216	neutral	None	None	None	None	I
D/L	0.7245	likely_pathogenic	0.7737	pathogenic	0.158	Stabilizing	0.826	D	0.5	neutral	None	None	None	None	I
D/M	0.7832	likely_pathogenic	0.824	pathogenic	0.433	Stabilizing	0.991	D	0.573	neutral	None	None	None	None	I
D/N	0.1747	likely_benign	0.2002	benign	0.011	Stabilizing	0.505	D	0.421	neutral	N	0.44152981	None	None	I
D/P	0.9837	likely_pathogenic	0.9857	pathogenic	0.009	Stabilizing	0.906	D	0.367	neutral	None	None	None	None	I
D/Q	0.4556	ambiguous	0.5181	ambiguous	0.042	Stabilizing	0.404	N	0.369	neutral	None	None	None	None	I
D/R	0.7536	likely_pathogenic	0.7924	pathogenic	0.386	Stabilizing	0.704	D	0.445	neutral	None	None	None	None	I
D/S	0.2165	likely_benign	0.2517	benign	-0.093	Destabilizing	0.404	N	0.331	neutral	None	None	None	None	I
D/T	0.4217	ambiguous	0.4726	ambiguous	0.074	Stabilizing	0.575	D	0.375	neutral	None	None	None	None	I
D/V	0.5281	ambiguous	0.5747	pathogenic	0.009	Stabilizing	0.782	D	0.5	neutral	N	0.495172294	None	None	I
D/W	0.9731	likely_pathogenic	0.9789	pathogenic	-0.224	Destabilizing	0.991	D	0.68	prob.neutral	None	None	None	None	I
D/Y	0.5559	ambiguous	0.6171	pathogenic	-0.112	Destabilizing	0.957	D	0.573	neutral	N	0.50092483	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.