TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15183	45772;45773;45774	chr2:178621171;178621170;178621169	chr2:179485898;179485897;179485896
N2AB	13542	40849;40850;40851	chr2:178621171;178621170;178621169	chr2:179485898;179485897;179485896
N2A	12615	38068;38069;38070	chr2:178621171;178621170;178621169	chr2:179485898;179485897;179485896
N2B	6118	18577;18578;18579	chr2:178621171;178621170;178621169	chr2:179485898;179485897;179485896
Novex-1	6243	18952;18953;18954	chr2:178621171;178621170;178621169	chr2:179485898;179485897;179485896
Novex-2	6310	19153;19154;19155	chr2:178621171;178621170;178621169	chr2:179485898;179485897;179485896
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-103
• Domain position: 64
• Structural Position: 146
• Q(SASA): 0.5691
• 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
L/V	None	None	0.046	N	0.262	0.039	0.20549828249	gnomAD-4.0.0	1.59365E-06	None	None	None	None	I	None	0	0	None	0	2.78878E-05	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
L/A	0.2758	likely_benign	0.2233	benign	-0.901	Destabilizing	0.91	D	0.397	neutral	None	None	None	None	I
L/C	0.7475	likely_pathogenic	0.709	pathogenic	-0.543	Destabilizing	0.999	D	0.481	neutral	None	None	None	None	I
L/D	0.7824	likely_pathogenic	0.7437	pathogenic	-0.518	Destabilizing	0.993	D	0.615	neutral	None	None	None	None	I
L/E	0.4363	ambiguous	0.3755	ambiguous	-0.615	Destabilizing	0.993	D	0.62	neutral	None	None	None	None	I
L/F	0.2271	likely_benign	0.2051	benign	-0.894	Destabilizing	0.991	D	0.395	neutral	N	0.457157006	None	None	I
L/G	0.6342	likely_pathogenic	0.5486	ambiguous	-1.09	Destabilizing	0.993	D	0.618	neutral	None	None	None	None	I
L/H	0.3231	likely_benign	0.3201	benign	-0.37	Destabilizing	0.999	D	0.615	neutral	None	None	None	None	I
L/I	0.1074	likely_benign	0.0994	benign	-0.515	Destabilizing	0.885	D	0.333	neutral	N	0.452923142	None	None	I
L/K	0.2532	likely_benign	0.2232	benign	-0.523	Destabilizing	0.993	D	0.549	neutral	None	None	None	None	I
L/M	0.161	likely_benign	0.1447	benign	-0.377	Destabilizing	0.993	D	0.436	neutral	None	None	None	None	I
L/N	0.5105	ambiguous	0.4362	ambiguous	-0.212	Destabilizing	0.998	D	0.619	neutral	None	None	None	None	I
L/P	0.2452	likely_benign	0.1964	benign	-0.611	Destabilizing	0.128	N	0.38	neutral	None	None	None	None	I
L/Q	0.1795	likely_benign	0.1657	benign	-0.497	Destabilizing	0.998	D	0.548	neutral	None	None	None	None	I
L/R	0.2049	likely_benign	0.2039	benign	0.118	Stabilizing	0.993	D	0.553	neutral	None	None	None	None	I
L/S	0.3094	likely_benign	0.268	benign	-0.664	Destabilizing	0.991	D	0.518	neutral	N	0.453918584	None	None	I
L/T	0.2804	likely_benign	0.2321	benign	-0.657	Destabilizing	0.986	D	0.401	neutral	None	None	None	None	I
L/V	0.1184	likely_benign	0.1038	benign	-0.611	Destabilizing	0.046	N	0.262	neutral	N	0.447697883	None	None	I
L/W	0.403	ambiguous	0.4207	ambiguous	-0.892	Destabilizing	0.999	D	0.597	neutral	None	None	None	None	I
L/Y	0.5193	ambiguous	0.4901	ambiguous	-0.655	Destabilizing	0.998	D	0.456	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.