TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28378	85357;85358;85359	chr2:178561000;178560999;178560998	chr2:179425727;179425726;179425725
N2AB	26737	80434;80435;80436	chr2:178561000;178560999;178560998	chr2:179425727;179425726;179425725
N2A	25810	77653;77654;77655	chr2:178561000;178560999;178560998	chr2:179425727;179425726;179425725
N2B	19313	58162;58163;58164	chr2:178561000;178560999;178560998	chr2:179425727;179425726;179425725
Novex-1	19438	58537;58538;58539	chr2:178561000;178560999;178560998	chr2:179425727;179425726;179425725
Novex-2	19505	58738;58739;58740	chr2:178561000;178560999;178560998	chr2:179425727;179425726;179425725
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-143
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.6236
• 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
N/K	rs1575618109	None	0.491	N	0.381	0.193	0.151104730317	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
N/S	None	None	0.166	N	0.429	0.167	0.134241683229	gnomAD-4.0.0	1.59115E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85806E-06	0	0
N/Y	rs1165610195	0.041	0.629	N	0.601	0.17	0.410204130746	gnomAD-4.0.0	5.47351E-06	None	None	None	None	I	None	1.49388E-04	0	None	0	0	None	0	0	0	0	4.96936E-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
N/A	0.1497	likely_benign	0.1564	benign	-1.021	Destabilizing	0.017	N	0.347	neutral	None	None	None	None	I
N/C	0.1726	likely_benign	0.1861	benign	-0.133	Destabilizing	0.991	D	0.599	neutral	None	None	None	None	I
N/D	0.1054	likely_benign	0.1008	benign	-1.107	Destabilizing	0.001	N	0.146	neutral	N	0.395627815	None	None	I
N/E	0.2622	likely_benign	0.2679	benign	-0.905	Destabilizing	0.209	N	0.402	neutral	None	None	None	None	I
N/F	0.404	ambiguous	0.4311	ambiguous	-0.394	Destabilizing	0.901	D	0.613	neutral	None	None	None	None	I
N/G	0.2076	likely_benign	0.2103	benign	-1.448	Destabilizing	0.345	N	0.401	neutral	None	None	None	None	I
N/H	0.0703	likely_benign	0.0756	benign	-1.004	Destabilizing	0.007	N	0.273	neutral	N	0.475763467	None	None	I
N/I	0.1743	likely_benign	0.1775	benign	0.119	Stabilizing	0.873	D	0.623	neutral	N	0.513108346	None	None	I
N/K	0.2122	likely_benign	0.2149	benign	-0.469	Destabilizing	0.491	N	0.381	neutral	N	0.450961023	None	None	I
N/L	0.1883	likely_benign	0.1915	benign	0.119	Stabilizing	0.561	D	0.555	neutral	None	None	None	None	I
N/M	0.2636	likely_benign	0.2677	benign	0.445	Stabilizing	0.991	D	0.585	neutral	None	None	None	None	I
N/P	0.3791	ambiguous	0.4057	ambiguous	-0.232	Destabilizing	0.004	N	0.357	neutral	None	None	None	None	I
N/Q	0.2233	likely_benign	0.2317	benign	-0.91	Destabilizing	0.818	D	0.469	neutral	None	None	None	None	I
N/R	0.2196	likely_benign	0.2316	benign	-0.71	Destabilizing	0.561	D	0.437	neutral	None	None	None	None	I
N/S	0.0645	likely_benign	0.0674	benign	-1.292	Destabilizing	0.166	N	0.429	neutral	N	0.452038458	None	None	I
N/T	0.0927	likely_benign	0.0961	benign	-0.888	Destabilizing	0.491	N	0.383	neutral	N	0.437242364	None	None	I
N/V	0.1697	likely_benign	0.1762	benign	-0.232	Destabilizing	0.561	D	0.579	neutral	None	None	None	None	I
N/W	0.6132	likely_pathogenic	0.6452	pathogenic	-0.23	Destabilizing	0.991	D	0.639	neutral	None	None	None	None	I
N/Y	0.1177	likely_benign	0.1259	benign	0.013	Stabilizing	0.629	D	0.601	neutral	N	0.486537821	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.