TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14346	43261;43262;43263	chr2:178633237;178633236;178633235	chr2:179497964;179497963;179497962
N2AB	12705	38338;38339;38340	chr2:178633237;178633236;178633235	chr2:179497964;179497963;179497962
N2A	11778	35557;35558;35559	chr2:178633237;178633236;178633235	chr2:179497964;179497963;179497962
N2B	5281	16066;16067;16068	chr2:178633237;178633236;178633235	chr2:179497964;179497963;179497962
Novex-1	5406	16441;16442;16443	chr2:178633237;178633236;178633235	chr2:179497964;179497963;179497962
Novex-2	5473	16642;16643;16644	chr2:178633237;178633236;178633235	chr2:179497964;179497963;179497962
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-94
• Domain position: 28
• Structural Position: 43
• Q(SASA): 0.2146
• 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
D/H	None	None	0.993	D	0.832	0.382	0.208816687407	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.93751E-06	0	0
D/N	None	None	0.987	N	0.785	0.307	0.146414634003	gnomAD-4.0.0	9.6026E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.05E-05	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	0.4195	ambiguous	0.3355	benign	-0.158	Destabilizing	0.974	D	0.773	deleterious	D	0.556038637	None	None	N
D/C	0.9118	likely_pathogenic	0.8774	pathogenic	-0.222	Destabilizing	0.999	D	0.818	deleterious	None	None	None	None	N
D/E	0.4204	ambiguous	0.3515	ambiguous	-0.145	Destabilizing	0.955	D	0.587	neutral	N	0.443807199	None	None	N
D/F	0.8313	likely_pathogenic	0.7664	pathogenic	-0.171	Destabilizing	0.961	D	0.851	deleterious	None	None	None	None	N
D/G	0.3008	likely_benign	0.2342	benign	-0.308	Destabilizing	0.955	D	0.801	deleterious	N	0.432104751	None	None	N
D/H	0.6083	likely_pathogenic	0.5318	ambiguous	0.288	Stabilizing	0.993	D	0.832	deleterious	D	0.599386263	None	None	N
D/I	0.79	likely_pathogenic	0.6893	pathogenic	0.18	Stabilizing	0.98	D	0.878	deleterious	None	None	None	None	N
D/K	0.748	likely_pathogenic	0.6549	pathogenic	0.129	Stabilizing	0.99	D	0.853	deleterious	None	None	None	None	N
D/L	0.7228	likely_pathogenic	0.6419	pathogenic	0.18	Stabilizing	0.961	D	0.844	deleterious	None	None	None	None	N
D/M	0.9028	likely_pathogenic	0.8554	pathogenic	0.019	Stabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
D/N	0.1882	likely_benign	0.1555	benign	0.039	Stabilizing	0.987	D	0.785	deleterious	N	0.461977751	None	None	N
D/P	0.9315	likely_pathogenic	0.8918	pathogenic	0.087	Stabilizing	0.997	D	0.83	deleterious	None	None	None	None	N
D/Q	0.7271	likely_pathogenic	0.6433	pathogenic	0.053	Stabilizing	0.99	D	0.778	deleterious	None	None	None	None	N
D/R	0.7612	likely_pathogenic	0.6777	pathogenic	0.42	Stabilizing	0.99	D	0.889	deleterious	None	None	None	None	N
D/S	0.2951	likely_benign	0.2392	benign	-0.135	Destabilizing	0.99	D	0.809	deleterious	None	None	None	None	N
D/T	0.5612	ambiguous	0.4738	ambiguous	-0.022	Destabilizing	0.99	D	0.855	deleterious	None	None	None	None	N
D/V	0.597	likely_pathogenic	0.495	ambiguous	0.087	Stabilizing	0.974	D	0.855	deleterious	N	0.51852576	None	None	N
D/W	0.9693	likely_pathogenic	0.9576	pathogenic	-0.098	Destabilizing	0.997	D	0.819	deleterious	None	None	None	None	N
D/Y	0.4798	ambiguous	0.4091	ambiguous	0.046	Stabilizing	0.071	N	0.559	neutral	D	0.560463216	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.