TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2770	8533;8534;8535	chr2:178770484;178770483;178770482	chr2:179635211;179635210;179635209
N2AB	2770	8533;8534;8535	chr2:178770484;178770483;178770482	chr2:179635211;179635210;179635209
N2A	2770	8533;8534;8535	chr2:178770484;178770483;178770482	chr2:179635211;179635210;179635209
N2B	2724	8395;8396;8397	chr2:178770484;178770483;178770482	chr2:179635211;179635210;179635209
Novex-1	2724	8395;8396;8397	chr2:178770484;178770483;178770482	chr2:179635211;179635210;179635209
Novex-2	2724	8395;8396;8397	chr2:178770484;178770483;178770482	chr2:179635211;179635210;179635209
Novex-3	2770	8533;8534;8535	chr2:178770484;178770483;178770482	chr2:179635211;179635210;179635209

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-17
• Domain position: 64
• Structural Position: 145
• Q(SASA): 0.2379
• 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
A/V	rs1329726455	None	None	N	0.152	0.115	0.313518423057	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
A/V	rs1329726455	None	None	N	0.152	0.115	0.313518423057	gnomAD-4.0.0	1.23906E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.69489E-06	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
A/C	0.3667	ambiguous	0.3632	ambiguous	-0.667	Destabilizing	0.002	N	0.285	neutral	None	None	None	None	I
A/D	0.2015	likely_benign	0.1964	benign	-0.86	Destabilizing	0.001	N	0.297	neutral	N	0.501065761	None	None	I
A/E	0.2005	likely_benign	0.193	benign	-1.018	Destabilizing	0.124	N	0.399	neutral	None	None	None	None	I
A/F	0.2614	likely_benign	0.2773	benign	-1.108	Destabilizing	0.497	N	0.452	neutral	None	None	None	None	I
A/G	0.1179	likely_benign	0.1224	benign	-0.543	Destabilizing	0.081	N	0.333	neutral	N	0.511490213	None	None	I
A/H	0.3542	ambiguous	0.3391	benign	-0.67	Destabilizing	0.667	D	0.439	neutral	None	None	None	None	I
A/I	0.1842	likely_benign	0.1835	benign	-0.456	Destabilizing	0.046	N	0.396	neutral	None	None	None	None	I
A/K	0.3054	likely_benign	0.2843	benign	-0.832	Destabilizing	0.22	N	0.388	neutral	None	None	None	None	I
A/L	0.1308	likely_benign	0.1352	benign	-0.456	Destabilizing	0.055	N	0.372	neutral	None	None	None	None	I
A/M	0.1661	likely_benign	0.1579	benign	-0.277	Destabilizing	0.497	N	0.382	neutral	None	None	None	None	I
A/N	0.1465	likely_benign	0.138	benign	-0.426	Destabilizing	0.004	N	0.224	neutral	None	None	None	None	I
A/P	0.5081	ambiguous	0.5244	ambiguous	-0.424	Destabilizing	0.602	D	0.387	neutral	N	0.505451618	None	None	I
A/Q	0.2405	likely_benign	0.2245	benign	-0.759	Destabilizing	0.667	D	0.384	neutral	None	None	None	None	I
A/R	0.2769	likely_benign	0.2533	benign	-0.303	Destabilizing	0.497	N	0.386	neutral	None	None	None	None	I
A/S	0.0752	likely_benign	0.0743	benign	-0.595	Destabilizing	0.042	N	0.376	neutral	N	0.450708242	None	None	I
A/T	0.0705	likely_benign	0.0671	benign	-0.684	Destabilizing	0.001	N	0.223	neutral	N	0.461279095	None	None	I
A/V	0.0997	likely_benign	0.1015	benign	-0.424	Destabilizing	None	N	0.152	neutral	N	0.474903754	None	None	I
A/W	0.7022	likely_pathogenic	0.7055	pathogenic	-1.263	Destabilizing	0.958	D	0.521	neutral	None	None	None	None	I
A/Y	0.3985	ambiguous	0.4222	ambiguous	-0.918	Destabilizing	0.667	D	0.449	neutral	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.