TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25373	76342;76343;76344	chr2:178570015;178570014;178570013	chr2:179434742;179434741;179434740
N2AB	23732	71419;71420;71421	chr2:178570015;178570014;178570013	chr2:179434742;179434741;179434740
N2A	22805	68638;68639;68640	chr2:178570015;178570014;178570013	chr2:179434742;179434741;179434740
N2B	16308	49147;49148;49149	chr2:178570015;178570014;178570013	chr2:179434742;179434741;179434740
Novex-1	16433	49522;49523;49524	chr2:178570015;178570014;178570013	chr2:179434742;179434741;179434740
Novex-2	16500	49723;49724;49725	chr2:178570015;178570014;178570013	chr2:179434742;179434741;179434740
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: Fn3-72
• Domain position: 70
• Structural Position: 102
• Q(SASA): 0.3382
• Predicted PPI site: N

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/Q	rs764739209	-0.625	0.951	N	0.376	0.246	0.251639045875	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
H/Q	rs764739209	-0.625	0.951	N	0.376	0.246	0.251639045875	gnomAD-4.0.0	3.4227E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.64048E-05	1.65728E-05

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	0.7534	likely_pathogenic	0.7357	pathogenic	-0.751	Destabilizing	0.373	N	0.329	neutral	None	None	None	None	N
H/C	0.2662	likely_benign	0.2732	benign	0.222	Stabilizing	0.996	D	0.488	neutral	None	None	None	None	N
H/D	0.7493	likely_pathogenic	0.7405	pathogenic	-0.755	Destabilizing	0.684	D	0.361	neutral	N	0.484255573	None	None	N
H/E	0.7691	likely_pathogenic	0.7319	pathogenic	-0.641	Destabilizing	0.742	D	0.325	neutral	None	None	None	None	N
H/F	0.7513	likely_pathogenic	0.7232	pathogenic	0.603	Stabilizing	0.953	D	0.38	neutral	None	None	None	None	N
H/G	0.724	likely_pathogenic	0.7032	pathogenic	-1.124	Destabilizing	0.59	D	0.352	neutral	None	None	None	None	N
H/I	0.8185	likely_pathogenic	0.808	pathogenic	0.296	Stabilizing	0.953	D	0.479	neutral	None	None	None	None	N
H/K	0.4443	ambiguous	0.4038	ambiguous	-0.42	Destabilizing	0.59	D	0.301	neutral	None	None	None	None	N
H/L	0.4819	ambiguous	0.4932	ambiguous	0.296	Stabilizing	0.684	D	0.44	neutral	N	0.506781728	None	None	N
H/M	0.8448	likely_pathogenic	0.8334	pathogenic	0.215	Stabilizing	0.996	D	0.421	neutral	None	None	None	None	N
H/N	0.3241	likely_benign	0.3273	benign	-0.554	Destabilizing	0.684	D	0.405	neutral	N	0.453005958	None	None	N
H/P	0.9264	likely_pathogenic	0.9292	pathogenic	-0.035	Destabilizing	0.939	D	0.426	neutral	N	0.502866807	None	None	N
H/Q	0.442	ambiguous	0.4137	ambiguous	-0.255	Destabilizing	0.951	D	0.376	neutral	N	0.473495874	None	None	N
H/R	0.1339	likely_benign	0.1215	benign	-0.988	Destabilizing	0.007	N	0.232	neutral	N	0.458641064	None	None	N
H/S	0.6346	likely_pathogenic	0.6135	pathogenic	-0.508	Destabilizing	0.037	N	0.243	neutral	None	None	None	None	N
H/T	0.7252	likely_pathogenic	0.6967	pathogenic	-0.298	Destabilizing	0.59	D	0.4	neutral	None	None	None	None	N
H/V	0.7315	likely_pathogenic	0.7165	pathogenic	-0.035	Destabilizing	0.91	D	0.443	neutral	None	None	None	None	N
H/W	0.7304	likely_pathogenic	0.7193	pathogenic	0.811	Stabilizing	0.996	D	0.5	neutral	None	None	None	None	N
H/Y	0.3343	likely_benign	0.3295	benign	0.879	Stabilizing	0.979	D	0.417	neutral	N	0.473659736	None	None	N

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.