TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27646	83161;83162;83163	chr2:178563196;178563195;178563194	chr2:179427923;179427922;179427921
N2AB	26005	78238;78239;78240	chr2:178563196;178563195;178563194	chr2:179427923;179427922;179427921
N2A	25078	75457;75458;75459	chr2:178563196;178563195;178563194	chr2:179427923;179427922;179427921
N2B	18581	55966;55967;55968	chr2:178563196;178563195;178563194	chr2:179427923;179427922;179427921
Novex-1	18706	56341;56342;56343	chr2:178563196;178563195;178563194	chr2:179427923;179427922;179427921
Novex-2	18773	56542;56543;56544	chr2:178563196;178563195;178563194	chr2:179427923;179427922;179427921
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-89
• Domain position: 77
• Structural Position: 108
• Q(SASA): 0.0605
• 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
I/V	None	None	0.011	N	0.202	0.064	0.313210971179	gnomAD-4.0.0	1.59135E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85865E-06	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
I/A	0.9587	likely_pathogenic	0.9579	pathogenic	-3.173	Highly Destabilizing	0.845	D	0.667	neutral	None	None	None	None	N
I/C	0.9504	likely_pathogenic	0.9512	pathogenic	-2.42	Highly Destabilizing	0.999	D	0.724	prob.delet.	None	None	None	None	N
I/D	0.9993	likely_pathogenic	0.9991	pathogenic	-3.809	Highly Destabilizing	0.996	D	0.867	deleterious	None	None	None	None	N
I/E	0.9982	likely_pathogenic	0.9979	pathogenic	-3.515	Highly Destabilizing	0.987	D	0.862	deleterious	None	None	None	None	N
I/F	0.6971	likely_pathogenic	0.7199	pathogenic	-1.798	Destabilizing	0.967	D	0.627	neutral	N	0.518687473	None	None	N
I/G	0.9943	likely_pathogenic	0.9941	pathogenic	-3.727	Highly Destabilizing	0.987	D	0.857	deleterious	None	None	None	None	N
I/H	0.9968	likely_pathogenic	0.9964	pathogenic	-3.214	Highly Destabilizing	0.999	D	0.863	deleterious	None	None	None	None	N
I/K	0.9967	likely_pathogenic	0.9961	pathogenic	-2.533	Highly Destabilizing	0.987	D	0.863	deleterious	None	None	None	None	N
I/L	0.3562	ambiguous	0.3473	ambiguous	-1.491	Destabilizing	0.426	N	0.317	neutral	N	0.519444381	None	None	N
I/M	0.5295	ambiguous	0.5493	ambiguous	-1.689	Destabilizing	0.983	D	0.63	neutral	N	0.496063767	None	None	N
I/N	0.9882	likely_pathogenic	0.9856	pathogenic	-3.147	Highly Destabilizing	0.994	D	0.875	deleterious	D	0.530804247	None	None	N
I/P	0.996	likely_pathogenic	0.9962	pathogenic	-2.046	Highly Destabilizing	0.996	D	0.877	deleterious	None	None	None	None	N
I/Q	0.9967	likely_pathogenic	0.9962	pathogenic	-2.863	Highly Destabilizing	0.996	D	0.882	deleterious	None	None	None	None	N
I/R	0.9942	likely_pathogenic	0.9928	pathogenic	-2.363	Highly Destabilizing	0.987	D	0.877	deleterious	None	None	None	None	N
I/S	0.9807	likely_pathogenic	0.977	pathogenic	-3.696	Highly Destabilizing	0.983	D	0.807	deleterious	N	0.519447941	None	None	N
I/T	0.9594	likely_pathogenic	0.9564	pathogenic	-3.265	Highly Destabilizing	0.892	D	0.68	prob.neutral	N	0.519194452	None	None	N
I/V	0.1028	likely_benign	0.1125	benign	-2.046	Highly Destabilizing	0.011	N	0.202	neutral	N	0.379875558	None	None	N
I/W	0.9955	likely_pathogenic	0.9955	pathogenic	-2.208	Highly Destabilizing	0.999	D	0.835	deleterious	None	None	None	None	N
I/Y	0.9739	likely_pathogenic	0.9716	pathogenic	-2.099	Highly Destabilizing	0.987	D	0.708	prob.delet.	None	None	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.