TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16736	50431;50432;50433	chr2:178612319;178612318;178612317	chr2:179477046;179477045;179477044
N2AB	15095	45508;45509;45510	chr2:178612319;178612318;178612317	chr2:179477046;179477045;179477044
N2A	14168	42727;42728;42729	chr2:178612319;178612318;178612317	chr2:179477046;179477045;179477044
N2B	7671	23236;23237;23238	chr2:178612319;178612318;178612317	chr2:179477046;179477045;179477044
Novex-1	7796	23611;23612;23613	chr2:178612319;178612318;178612317	chr2:179477046;179477045;179477044
Novex-2	7863	23812;23813;23814	chr2:178612319;178612318;178612317	chr2:179477046;179477045;179477044
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-9
• Domain position: 86
• Structural Position: 120
• Q(SASA): 0.3041
• 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
Y/N	None	None	0.998	N	0.721	0.535	0.676040837911	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
Y/A	0.9334	likely_pathogenic	0.9005	pathogenic	-2.571	Highly Destabilizing	0.985	D	0.603	neutral	None	None	None	None	N
Y/C	0.6976	likely_pathogenic	0.5962	pathogenic	-1.055	Destabilizing	1.0	D	0.734	prob.delet.	N	0.473627848	None	None	N
Y/D	0.9366	likely_pathogenic	0.9178	pathogenic	-2.599	Highly Destabilizing	0.998	D	0.743	deleterious	N	0.466157378	None	None	N
Y/E	0.9888	likely_pathogenic	0.9837	pathogenic	-2.431	Highly Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
Y/F	0.0983	likely_benign	0.0866	benign	-0.851	Destabilizing	0.031	N	0.253	neutral	N	0.385766822	None	None	N
Y/G	0.9331	likely_pathogenic	0.9137	pathogenic	-2.938	Highly Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
Y/H	0.8164	likely_pathogenic	0.7586	pathogenic	-1.485	Destabilizing	0.998	D	0.649	neutral	N	0.475897517	None	None	N
Y/I	0.9291	likely_pathogenic	0.9027	pathogenic	-1.376	Destabilizing	0.97	D	0.626	neutral	None	None	None	None	N
Y/K	0.9878	likely_pathogenic	0.9848	pathogenic	-1.485	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
Y/L	0.8835	likely_pathogenic	0.8611	pathogenic	-1.376	Destabilizing	0.871	D	0.571	neutral	None	None	None	None	N
Y/M	0.9481	likely_pathogenic	0.9307	pathogenic	-1.003	Destabilizing	0.999	D	0.726	prob.delet.	None	None	None	None	N
Y/N	0.8338	likely_pathogenic	0.7867	pathogenic	-2.108	Highly Destabilizing	0.998	D	0.721	prob.delet.	N	0.465652718	None	None	N
Y/P	0.8949	likely_pathogenic	0.8435	pathogenic	-1.783	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
Y/Q	0.9853	likely_pathogenic	0.9781	pathogenic	-1.961	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
Y/R	0.9723	likely_pathogenic	0.9659	pathogenic	-1.18	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
Y/S	0.8367	likely_pathogenic	0.7804	pathogenic	-2.477	Highly Destabilizing	0.998	D	0.668	neutral	N	0.473287673	None	None	N
Y/T	0.947	likely_pathogenic	0.9284	pathogenic	-2.206	Highly Destabilizing	0.999	D	0.668	neutral	None	None	None	None	N
Y/V	0.8772	likely_pathogenic	0.8314	pathogenic	-1.783	Destabilizing	0.97	D	0.571	neutral	None	None	None	None	N
Y/W	0.6006	likely_pathogenic	0.5798	pathogenic	-0.267	Destabilizing	0.999	D	0.657	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.