TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27117	81574;81575;81576	chr2:178564783;178564782;178564781	chr2:179429510;179429509;179429508
N2AB	25476	76651;76652;76653	chr2:178564783;178564782;178564781	chr2:179429510;179429509;179429508
N2A	24549	73870;73871;73872	chr2:178564783;178564782;178564781	chr2:179429510;179429509;179429508
N2B	18052	54379;54380;54381	chr2:178564783;178564782;178564781	chr2:179429510;179429509;179429508
Novex-1	18177	54754;54755;54756	chr2:178564783;178564782;178564781	chr2:179429510;179429509;179429508
Novex-2	18244	54955;54956;54957	chr2:178564783;178564782;178564781	chr2:179429510;179429509;179429508
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: Fn3-85
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.9471
• 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
I/T	rs1326162454	-0.344	0.99	N	0.561	0.393	0.615732620514	gnomAD-2.1.1	4.1E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.29E-05	None	0	0	0
I/T	rs1326162454	-0.344	0.99	N	0.561	0.393	0.615732620514	gnomAD-4.0.0	3.19026E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.87183E-05	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	0.8846	likely_pathogenic	0.844	pathogenic	-0.525	Destabilizing	0.993	D	0.55	neutral	None	None	None	None	I
I/C	0.9644	likely_pathogenic	0.953	pathogenic	-0.89	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	I
I/D	0.9814	likely_pathogenic	0.972	pathogenic	-0.179	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	I
I/E	0.9801	likely_pathogenic	0.9684	pathogenic	-0.257	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	I
I/F	0.55	ambiguous	0.4858	ambiguous	-0.645	Destabilizing	0.994	D	0.583	neutral	N	0.479091012	None	None	I
I/G	0.9722	likely_pathogenic	0.9597	pathogenic	-0.619	Destabilizing	0.999	D	0.638	neutral	None	None	None	None	I
I/H	0.9451	likely_pathogenic	0.9263	pathogenic	0.08	Stabilizing	1.0	D	0.657	neutral	None	None	None	None	I
I/K	0.9388	likely_pathogenic	0.9111	pathogenic	-0.387	Destabilizing	0.999	D	0.639	neutral	None	None	None	None	I
I/L	0.1909	likely_benign	0.153	benign	-0.385	Destabilizing	0.061	N	0.262	neutral	N	0.452024523	None	None	I
I/M	0.3533	ambiguous	0.2965	benign	-0.712	Destabilizing	0.994	D	0.581	neutral	N	0.514054417	None	None	I
I/N	0.8707	likely_pathogenic	0.8279	pathogenic	-0.3	Destabilizing	0.999	D	0.653	neutral	N	0.474975954	None	None	I
I/P	0.916	likely_pathogenic	0.9015	pathogenic	-0.406	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	I
I/Q	0.9501	likely_pathogenic	0.9295	pathogenic	-0.441	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	I
I/R	0.8825	likely_pathogenic	0.8435	pathogenic	0.051	Stabilizing	0.999	D	0.65	neutral	None	None	None	None	I
I/S	0.8617	likely_pathogenic	0.8187	pathogenic	-0.702	Destabilizing	0.999	D	0.579	neutral	N	0.475842745	None	None	I
I/T	0.9153	likely_pathogenic	0.8879	pathogenic	-0.682	Destabilizing	0.99	D	0.561	neutral	N	0.502239913	None	None	I
I/V	0.2473	likely_benign	0.2081	benign	-0.406	Destabilizing	0.817	D	0.503	neutral	N	0.488118609	None	None	I
I/W	0.9555	likely_pathogenic	0.9457	pathogenic	-0.652	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	I
I/Y	0.8517	likely_pathogenic	0.8232	pathogenic	-0.441	Destabilizing	0.999	D	0.605	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.