TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20271	61036;61037;61038	chr2:178590914;178590913;178590912	chr2:179455641;179455640;179455639
N2AB	18630	56113;56114;56115	chr2:178590914;178590913;178590912	chr2:179455641;179455640;179455639
N2A	17703	53332;53333;53334	chr2:178590914;178590913;178590912	chr2:179455641;179455640;179455639
N2B	11206	33841;33842;33843	chr2:178590914;178590913;178590912	chr2:179455641;179455640;179455639
Novex-1	11331	34216;34217;34218	chr2:178590914;178590913;178590912	chr2:179455641;179455640;179455639
Novex-2	11398	34417;34418;34419	chr2:178590914;178590913;178590912	chr2:179455641;179455640;179455639
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-35
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.9492
• 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
P/R	rs367633145	0.495	0.993	N	0.821	0.334	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
P/R	rs367633145	0.495	0.993	N	0.821	0.334	None	gnomAD-4.0.0	3.84882E-06	None	None	None	None	I	None	3.3857E-05	0	None	0	0	None	0	0	0	0	2.84738E-05
P/T	rs886055256	None	0.953	N	0.608	0.335	0.339074221408	gnomAD-4.0.0	1.59373E-06	None	None	None	None	I	None	5.66572E-05	0	None	0	0	None	0	0	0	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
P/A	0.0901	likely_benign	0.0842	benign	-0.318	Destabilizing	0.214	N	0.344	neutral	N	0.499311464	None	None	I
P/C	0.3985	ambiguous	0.4156	ambiguous	-0.554	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	I
P/D	0.6848	likely_pathogenic	0.7141	pathogenic	0.009	Stabilizing	0.995	D	0.585	neutral	None	None	None	None	I
P/E	0.3136	likely_benign	0.3389	benign	-0.119	Destabilizing	0.995	D	0.561	neutral	None	None	None	None	I
P/F	0.5091	ambiguous	0.5504	ambiguous	-0.721	Destabilizing	0.995	D	0.821	deleterious	None	None	None	None	I
P/G	0.5267	ambiguous	0.5309	ambiguous	-0.405	Destabilizing	0.931	D	0.545	neutral	None	None	None	None	I
P/H	0.258	likely_benign	0.3036	benign	-0.064	Destabilizing	0.999	D	0.784	deleterious	N	0.488241591	None	None	I
P/I	0.1412	likely_benign	0.1586	benign	-0.25	Destabilizing	0.979	D	0.613	neutral	None	None	None	None	I
P/K	0.2911	likely_benign	0.3376	benign	-0.083	Destabilizing	0.99	D	0.549	neutral	None	None	None	None	I
P/L	0.1014	likely_benign	0.1124	benign	-0.25	Destabilizing	0.91	D	0.623	neutral	N	0.491694845	None	None	I
P/M	0.2571	likely_benign	0.2698	benign	-0.211	Destabilizing	0.999	D	0.752	deleterious	None	None	None	None	I
P/N	0.4821	ambiguous	0.5185	ambiguous	0.126	Stabilizing	0.998	D	0.826	deleterious	None	None	None	None	I
P/Q	0.1764	likely_benign	0.2054	benign	-0.137	Destabilizing	0.998	D	0.544	neutral	None	None	None	None	I
P/R	0.2048	likely_benign	0.2477	benign	0.362	Stabilizing	0.993	D	0.821	deleterious	N	0.499852969	None	None	I
P/S	0.1618	likely_benign	0.1682	benign	-0.243	Destabilizing	0.91	D	0.618	neutral	N	0.472984492	None	None	I
P/T	0.1036	likely_benign	0.1092	benign	-0.272	Destabilizing	0.953	D	0.608	neutral	N	0.486720654	None	None	I
P/V	0.1038	likely_benign	0.1128	benign	-0.24	Destabilizing	0.455	N	0.373	neutral	None	None	None	None	I
P/W	0.761	likely_pathogenic	0.8056	pathogenic	-0.776	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
P/Y	0.5094	ambiguous	0.5476	ambiguous	-0.439	Destabilizing	0.998	D	0.822	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.