TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31198	93817;93818;93819	chr2:178548034;178548033;178548032	chr2:179412761;179412760;179412759
N2AB	29557	88894;88895;88896	chr2:178548034;178548033;178548032	chr2:179412761;179412760;179412759
N2A	28630	86113;86114;86115	chr2:178548034;178548033;178548032	chr2:179412761;179412760;179412759
N2B	22133	66622;66623;66624	chr2:178548034;178548033;178548032	chr2:179412761;179412760;179412759
Novex-1	22258	66997;66998;66999	chr2:178548034;178548033;178548032	chr2:179412761;179412760;179412759
Novex-2	22325	67198;67199;67200	chr2:178548034;178548033;178548032	chr2:179412761;179412760;179412759
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-115
• Domain position: 86
• Structural Position: 121
• Q(SASA): 0.2263
• 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
R/G	rs751148256	-1.943	0.99	N	0.606	0.239	0.381746406553	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	5.8E-05	None	0	0	None	0	None	0	0	1.65673E-04
R/G	rs751148256	-1.943	0.99	N	0.606	0.239	0.381746406553	gnomAD-4.0.0	3.18228E-06	None	None	None	None	N	None	0	4.57373E-05	None	0	0	None	0	0	0	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
R/A	0.6658	likely_pathogenic	0.6403	pathogenic	-1.094	Destabilizing	0.985	D	0.549	neutral	None	None	None	None	N
R/C	0.3668	ambiguous	0.343	ambiguous	-1.13	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
R/D	0.9565	likely_pathogenic	0.9528	pathogenic	-0.377	Destabilizing	0.996	D	0.649	neutral	None	None	None	None	N
R/E	0.7312	likely_pathogenic	0.7246	pathogenic	-0.185	Destabilizing	0.971	D	0.507	neutral	None	None	None	None	N
R/F	0.911	likely_pathogenic	0.9101	pathogenic	-0.413	Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
R/G	0.6672	likely_pathogenic	0.6193	pathogenic	-1.471	Destabilizing	0.99	D	0.606	neutral	N	0.472781011	None	None	N
R/H	0.3713	ambiguous	0.3554	ambiguous	-1.548	Destabilizing	0.998	D	0.647	neutral	None	None	None	None	N
R/I	0.6704	likely_pathogenic	0.6524	pathogenic	-0.038	Destabilizing	0.999	D	0.735	prob.delet.	N	0.466121183	None	None	N
R/K	0.2362	likely_benign	0.2361	benign	-1.099	Destabilizing	0.911	D	0.5	neutral	N	0.482651288	None	None	N
R/L	0.6525	likely_pathogenic	0.6203	pathogenic	-0.038	Destabilizing	0.985	D	0.606	neutral	None	None	None	None	N
R/M	0.666	likely_pathogenic	0.6239	pathogenic	-0.553	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
R/N	0.9188	likely_pathogenic	0.9202	pathogenic	-0.851	Destabilizing	0.998	D	0.569	neutral	None	None	None	None	N
R/P	0.9774	likely_pathogenic	0.9689	pathogenic	-0.372	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
R/Q	0.1923	likely_benign	0.1875	benign	-0.745	Destabilizing	0.719	D	0.361	neutral	None	None	None	None	N
R/S	0.8023	likely_pathogenic	0.7669	pathogenic	-1.599	Destabilizing	0.98	D	0.584	neutral	N	0.379646271	None	None	N
R/T	0.5719	likely_pathogenic	0.5204	ambiguous	-1.198	Destabilizing	0.99	D	0.631	neutral	N	0.485766164	None	None	N
R/V	0.626	likely_pathogenic	0.6032	pathogenic	-0.372	Destabilizing	0.998	D	0.713	prob.delet.	None	None	None	None	N
R/W	0.5781	likely_pathogenic	0.5252	ambiguous	-0.015	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
R/Y	0.8288	likely_pathogenic	0.8252	pathogenic	0.211	Stabilizing	0.999	D	0.725	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.