TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31562	94909;94910;94911	chr2:178546744;178546743;178546742	chr2:179411471;179411470;179411469
N2AB	29921	89986;89987;89988	chr2:178546744;178546743;178546742	chr2:179411471;179411470;179411469
N2A	28994	87205;87206;87207	chr2:178546744;178546743;178546742	chr2:179411471;179411470;179411469
N2B	22497	67714;67715;67716	chr2:178546744;178546743;178546742	chr2:179411471;179411470;179411469
Novex-1	22622	68089;68090;68091	chr2:178546744;178546743;178546742	chr2:179411471;179411470;179411469
Novex-2	22689	68290;68291;68292	chr2:178546744;178546743;178546742	chr2:179411471;179411470;179411469
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-118
• Domain position: 57
• Structural Position: 72
• Q(SASA): 0.6992
• 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
T/A	None	None	0.981	N	0.609	0.357	0.317958651998	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
T/N	rs1697337398	None	0.999	N	0.65	0.384	0.551798466036	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/N	rs1697337398	None	0.999	N	0.65	0.384	0.551798466036	gnomAD-4.0.0	6.57592E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47063E-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
T/A	0.2387	likely_benign	0.1817	benign	-0.158	Destabilizing	0.981	D	0.609	neutral	N	0.503106705	None	None	I
T/C	0.8677	likely_pathogenic	0.8209	pathogenic	-0.413	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	I
T/D	0.9096	likely_pathogenic	0.8482	pathogenic	0.212	Stabilizing	0.999	D	0.625	neutral	None	None	None	None	I
T/E	0.8992	likely_pathogenic	0.8442	pathogenic	0.132	Stabilizing	0.999	D	0.624	neutral	None	None	None	None	I
T/F	0.8964	likely_pathogenic	0.8517	pathogenic	-0.799	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
T/G	0.5323	ambiguous	0.445	ambiguous	-0.233	Destabilizing	0.997	D	0.593	neutral	None	None	None	None	I
T/H	0.7946	likely_pathogenic	0.706	pathogenic	-0.382	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
T/I	0.7817	likely_pathogenic	0.7121	pathogenic	-0.087	Destabilizing	0.999	D	0.64	neutral	N	0.485347663	None	None	I
T/K	0.8416	likely_pathogenic	0.7613	pathogenic	-0.252	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	I
T/L	0.4912	ambiguous	0.3839	ambiguous	-0.087	Destabilizing	0.998	D	0.603	neutral	None	None	None	None	I
T/M	0.328	likely_benign	0.2635	benign	-0.208	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
T/N	0.4138	ambiguous	0.2994	benign	-0.136	Destabilizing	0.999	D	0.65	neutral	N	0.46930487	None	None	I
T/P	0.8298	likely_pathogenic	0.7376	pathogenic	-0.085	Destabilizing	0.999	D	0.633	neutral	N	0.484624421	None	None	I
T/Q	0.691	likely_pathogenic	0.6034	pathogenic	-0.292	Destabilizing	1.0	D	0.636	neutral	None	None	None	None	I
T/R	0.7838	likely_pathogenic	0.7043	pathogenic	0.004	Stabilizing	1.0	D	0.625	neutral	None	None	None	None	I
T/S	0.2831	likely_benign	0.2121	benign	-0.304	Destabilizing	0.905	D	0.427	neutral	N	0.467185977	None	None	I
T/V	0.5538	ambiguous	0.4852	ambiguous	-0.085	Destabilizing	0.998	D	0.621	neutral	None	None	None	None	I
T/W	0.9783	likely_pathogenic	0.9674	pathogenic	-0.898	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
T/Y	0.8958	likely_pathogenic	0.8488	pathogenic	-0.565	Destabilizing	1.0	D	0.704	prob.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.