TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28976	87151;87152;87153	chr2:178558533;178558532;178558531	chr2:179423260;179423259;179423258
N2AB	27335	82228;82229;82230	chr2:178558533;178558532;178558531	chr2:179423260;179423259;179423258
N2A	26408	79447;79448;79449	chr2:178558533;178558532;178558531	chr2:179423260;179423259;179423258
N2B	19911	59956;59957;59958	chr2:178558533;178558532;178558531	chr2:179423260;179423259;179423258
Novex-1	20036	60331;60332;60333	chr2:178558533;178558532;178558531	chr2:179423260;179423259;179423258
Novex-2	20103	60532;60533;60534	chr2:178558533;178558532;178558531	chr2:179423260;179423259;179423258
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Fn3-99
• Domain position: 35
• Structural Position: 37
• Q(SASA): 0.4232
• 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
H/P	rs1392632968	-0.128	0.784	N	0.553	0.259	0.47290127212	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	4.64E-05	0	0
H/P	rs1392632968	-0.128	0.784	N	0.553	0.259	0.47290127212	gnomAD-4.0.0	1.59137E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85814E-06	0	0
H/R	rs1392632968	None	0.642	N	0.355	0.18	0.279776271856	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
H/R	rs1392632968	None	0.642	N	0.355	0.18	0.279776271856	gnomAD-4.0.0	1.31334E-05	None	None	None	None	I	None	0	1.30856E-04	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
H/A	0.2328	likely_benign	0.1919	benign	-1.201	Destabilizing	0.085	N	0.34	neutral	None	None	None	None	I
H/C	0.124	likely_benign	0.1085	benign	-0.283	Destabilizing	0.981	D	0.488	neutral	None	None	None	None	I
H/D	0.2497	likely_benign	0.2144	benign	-0.912	Destabilizing	0.27	N	0.349	neutral	N	0.434862915	None	None	I
H/E	0.3811	ambiguous	0.3554	ambiguous	-0.767	Destabilizing	0.495	N	0.299	neutral	None	None	None	None	I
H/F	0.3482	ambiguous	0.3301	benign	0.431	Stabilizing	0.981	D	0.582	neutral	None	None	None	None	I
H/G	0.1644	likely_benign	0.1392	benign	-1.598	Destabilizing	0.001	N	0.243	neutral	None	None	None	None	I
H/I	0.569	likely_pathogenic	0.5234	ambiguous	-0.068	Destabilizing	0.828	D	0.602	neutral	None	None	None	None	I
H/K	0.3183	likely_benign	0.2935	benign	-0.863	Destabilizing	0.495	N	0.351	neutral	None	None	None	None	I
H/L	0.2092	likely_benign	0.1956	benign	-0.068	Destabilizing	0.425	N	0.422	neutral	N	0.51016875	None	None	I
H/M	0.5642	likely_pathogenic	0.5042	ambiguous	-0.224	Destabilizing	0.981	D	0.509	neutral	None	None	None	None	I
H/N	0.0792	likely_benign	0.0622	benign	-1.167	Destabilizing	0.01	N	0.121	neutral	N	0.393496295	None	None	I
H/P	0.8372	likely_pathogenic	0.8235	pathogenic	-0.429	Destabilizing	0.784	D	0.553	neutral	N	0.468495176	None	None	I
H/Q	0.1815	likely_benign	0.1586	benign	-0.844	Destabilizing	0.784	D	0.382	neutral	N	0.4662819	None	None	I
H/R	0.1233	likely_benign	0.1276	benign	-1.282	Destabilizing	0.642	D	0.355	neutral	N	0.438479223	None	None	I
H/S	0.1411	likely_benign	0.1084	benign	-1.221	Destabilizing	0.013	N	0.163	neutral	None	None	None	None	I
H/T	0.2684	likely_benign	0.2161	benign	-0.97	Destabilizing	0.329	N	0.377	neutral	None	None	None	None	I
H/V	0.4352	ambiguous	0.3923	ambiguous	-0.429	Destabilizing	0.704	D	0.479	neutral	None	None	None	None	I
H/W	0.481	ambiguous	0.4968	ambiguous	0.884	Stabilizing	0.995	D	0.515	neutral	None	None	None	None	I
H/Y	0.1048	likely_benign	0.1034	benign	0.819	Stabilizing	0.917	D	0.415	neutral	N	0.452179239	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.