TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25304	76135;76136;76137	chr2:178570222;178570221;178570220	chr2:179434949;179434948;179434947
N2AB	23663	71212;71213;71214	chr2:178570222;178570221;178570220	chr2:179434949;179434948;179434947
N2A	22736	68431;68432;68433	chr2:178570222;178570221;178570220	chr2:179434949;179434948;179434947
N2B	16239	48940;48941;48942	chr2:178570222;178570221;178570220	chr2:179434949;179434948;179434947
Novex-1	16364	49315;49316;49317	chr2:178570222;178570221;178570220	chr2:179434949;179434948;179434947
Novex-2	16431	49516;49517;49518	chr2:178570222;178570221;178570220	chr2:179434949;179434948;179434947
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-72
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.4944
• 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
V/E	None	None	0.335	N	0.418	0.209	0.647137792213	gnomAD-4.0.0	1.59198E-06	None	None	None	None	I	None	0	2.28781E-05	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
V/A	0.1388	likely_benign	0.1597	benign	-0.619	Destabilizing	0.006	N	0.072	neutral	N	0.515590425	None	None	I
V/C	0.6038	likely_pathogenic	0.6785	pathogenic	-0.647	Destabilizing	0.991	D	0.331	neutral	None	None	None	None	I
V/D	0.5479	ambiguous	0.543	ambiguous	-0.52	Destabilizing	0.004	N	0.213	neutral	None	None	None	None	I
V/E	0.3456	ambiguous	0.3681	ambiguous	-0.643	Destabilizing	0.335	N	0.418	neutral	N	0.4690117	None	None	I
V/F	0.2182	likely_benign	0.2175	benign	-1.045	Destabilizing	0.966	D	0.47	neutral	None	None	None	None	I
V/G	0.2632	likely_benign	0.2865	benign	-0.729	Destabilizing	0.501	D	0.421	neutral	N	0.511905708	None	None	I
V/H	0.5116	ambiguous	0.5558	ambiguous	-0.358	Destabilizing	0.991	D	0.333	neutral	None	None	None	None	I
V/I	0.0725	likely_benign	0.0767	benign	-0.479	Destabilizing	0.293	N	0.361	neutral	N	0.514438419	None	None	I
V/K	0.2014	likely_benign	0.2215	benign	-0.282	Destabilizing	0.571	D	0.396	neutral	None	None	None	None	I
V/L	0.1465	likely_benign	0.18	benign	-0.479	Destabilizing	0.293	N	0.387	neutral	N	0.504029424	None	None	I
V/M	0.1381	likely_benign	0.165	benign	-0.282	Destabilizing	0.966	D	0.367	neutral	None	None	None	None	I
V/N	0.3459	ambiguous	0.3738	ambiguous	-0.086	Destabilizing	0.7	D	0.401	neutral	None	None	None	None	I
V/P	0.1716	likely_benign	0.2073	benign	-0.493	Destabilizing	0.905	D	0.409	neutral	None	None	None	None	I
V/Q	0.2538	likely_benign	0.2901	benign	-0.421	Destabilizing	0.905	D	0.415	neutral	None	None	None	None	I
V/R	0.1979	likely_benign	0.2128	benign	0.227	Stabilizing	0.905	D	0.454	neutral	None	None	None	None	I
V/S	0.2282	likely_benign	0.2549	benign	-0.438	Destabilizing	0.216	N	0.357	neutral	None	None	None	None	I
V/T	0.1553	likely_benign	0.1717	benign	-0.47	Destabilizing	0.007	N	0.057	neutral	None	None	None	None	I
V/W	0.8159	likely_pathogenic	0.8321	pathogenic	-1.078	Destabilizing	0.991	D	0.421	neutral	None	None	None	None	I
V/Y	0.5629	ambiguous	0.5868	pathogenic	-0.73	Destabilizing	0.966	D	0.451	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.