TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22080	66463;66464;66465	chr2:178582131;178582130;178582129	chr2:179446858;179446857;179446856
N2AB	20439	61540;61541;61542	chr2:178582131;178582130;178582129	chr2:179446858;179446857;179446856
N2A	19512	58759;58760;58761	chr2:178582131;178582130;178582129	chr2:179446858;179446857;179446856
N2B	13015	39268;39269;39270	chr2:178582131;178582130;178582129	chr2:179446858;179446857;179446856
Novex-1	13140	39643;39644;39645	chr2:178582131;178582130;178582129	chr2:179446858;179446857;179446856
Novex-2	13207	39844;39845;39846	chr2:178582131;178582130;178582129	chr2:179446858;179446857;179446856
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-48
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.631
• 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
A/T	None	None	0.565	N	0.41	0.143	0.290222751274	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
A/C	0.4365	ambiguous	0.4006	ambiguous	-0.715	Destabilizing	0.996	D	0.439	neutral	None	None	None	None	N
A/D	0.2612	likely_benign	0.2505	benign	-0.562	Destabilizing	0.858	D	0.481	neutral	None	None	None	None	N
A/E	0.2031	likely_benign	0.205	benign	-0.725	Destabilizing	0.018	N	0.244	neutral	N	0.412698131	None	None	N
A/F	0.3578	ambiguous	0.3453	ambiguous	-0.939	Destabilizing	0.961	D	0.623	neutral	None	None	None	None	N
A/G	0.1404	likely_benign	0.1385	benign	-0.21	Destabilizing	0.565	D	0.407	neutral	N	0.479328555	None	None	N
A/H	0.4064	ambiguous	0.4059	ambiguous	-0.281	Destabilizing	0.989	D	0.609	neutral	None	None	None	None	N
A/I	0.158	likely_benign	0.1593	benign	-0.37	Destabilizing	0.858	D	0.391	neutral	None	None	None	None	N
A/K	0.2926	likely_benign	0.3094	benign	-0.533	Destabilizing	0.633	D	0.424	neutral	None	None	None	None	N
A/L	0.1303	likely_benign	0.1309	benign	-0.37	Destabilizing	0.633	D	0.431	neutral	None	None	None	None	N
A/M	0.1736	likely_benign	0.176	benign	-0.445	Destabilizing	0.989	D	0.484	neutral	None	None	None	None	N
A/N	0.2038	likely_benign	0.207	benign	-0.173	Destabilizing	0.858	D	0.614	neutral	None	None	None	None	N
A/P	0.1805	likely_benign	0.1905	benign	-0.285	Destabilizing	0.949	D	0.478	neutral	N	0.481982071	None	None	N
A/Q	0.2342	likely_benign	0.2471	benign	-0.471	Destabilizing	0.858	D	0.478	neutral	None	None	None	None	N
A/R	0.3257	likely_benign	0.3218	benign	-0.08	Destabilizing	0.923	D	0.477	neutral	None	None	None	None	N
A/S	0.0909	likely_benign	0.0909	benign	-0.327	Destabilizing	0.075	N	0.175	neutral	N	0.437268502	None	None	N
A/T	0.0747	likely_benign	0.0779	benign	-0.421	Destabilizing	0.565	D	0.41	neutral	N	0.472381153	None	None	N
A/V	0.0934	likely_benign	0.0979	benign	-0.285	Destabilizing	0.018	N	0.183	neutral	N	0.477808402	None	None	N
A/W	0.7004	likely_pathogenic	0.6679	pathogenic	-1.053	Destabilizing	0.996	D	0.696	prob.neutral	None	None	None	None	N
A/Y	0.4539	ambiguous	0.4351	ambiguous	-0.716	Destabilizing	0.987	D	0.61	neutral	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.