TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23915	71968;71969;71970	chr2:178574389;178574388;178574387	chr2:179439116;179439115;179439114
N2AB	22274	67045;67046;67047	chr2:178574389;178574388;178574387	chr2:179439116;179439115;179439114
N2A	21347	64264;64265;64266	chr2:178574389;178574388;178574387	chr2:179439116;179439115;179439114
N2B	14850	44773;44774;44775	chr2:178574389;178574388;178574387	chr2:179439116;179439115;179439114
Novex-1	14975	45148;45149;45150	chr2:178574389;178574388;178574387	chr2:179439116;179439115;179439114
Novex-2	15042	45349;45350;45351	chr2:178574389;178574388;178574387	chr2:179439116;179439115;179439114
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-61
• Domain position: 90
• Structural Position: 123
• Q(SASA): 0.367
• 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
P/T	None	None	0.376	N	0.494	0.1	0.226586394389	gnomAD-4.0.0	1.59179E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02444E-05

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
P/A	0.0602	likely_benign	0.0661	benign	-1.537	Destabilizing	0.004	N	0.327	neutral	N	0.466337828	None	None	I
P/C	0.3732	ambiguous	0.4102	ambiguous	-0.928	Destabilizing	0.977	D	0.777	deleterious	None	None	None	None	I
P/D	0.6777	likely_pathogenic	0.731	pathogenic	-1.207	Destabilizing	0.848	D	0.54	neutral	None	None	None	None	I
P/E	0.454	ambiguous	0.4952	ambiguous	-1.221	Destabilizing	0.615	D	0.512	neutral	None	None	None	None	I
P/F	0.487	ambiguous	0.5549	ambiguous	-1.24	Destabilizing	0.919	D	0.778	deleterious	None	None	None	None	I
P/G	0.3191	likely_benign	0.3641	ambiguous	-1.84	Destabilizing	0.444	N	0.614	neutral	None	None	None	None	I
P/H	0.315	likely_benign	0.3573	ambiguous	-1.295	Destabilizing	0.977	D	0.693	prob.delet.	None	None	None	None	I
P/I	0.1885	likely_benign	0.2062	benign	-0.81	Destabilizing	0.737	D	0.724	deleterious	None	None	None	None	I
P/K	0.5393	ambiguous	0.5485	ambiguous	-1.152	Destabilizing	0.444	N	0.52	neutral	None	None	None	None	I
P/L	0.1278	likely_benign	0.1384	benign	-0.81	Destabilizing	0.376	N	0.689	prob.delet.	N	0.518246728	None	None	I
P/M	0.2563	likely_benign	0.2766	benign	-0.586	Destabilizing	0.977	D	0.693	prob.delet.	None	None	None	None	I
P/N	0.3747	ambiguous	0.4307	ambiguous	-0.887	Destabilizing	0.737	D	0.657	prob.neutral	None	None	None	None	I
P/Q	0.2499	likely_benign	0.2665	benign	-1.095	Destabilizing	0.808	D	0.539	neutral	N	0.491902122	None	None	I
P/R	0.4175	ambiguous	0.4311	ambiguous	-0.588	Destabilizing	0.808	D	0.678	prob.neutral	N	0.500042423	None	None	I
P/S	0.1262	likely_benign	0.1425	benign	-1.422	Destabilizing	0.016	N	0.348	neutral	N	0.463478292	None	None	I
P/T	0.1011	likely_benign	0.106	benign	-1.329	Destabilizing	0.376	N	0.494	neutral	N	0.494620507	None	None	I
P/V	0.1286	likely_benign	0.1394	benign	-1.018	Destabilizing	0.011	N	0.544	neutral	None	None	None	None	I
P/W	0.7425	likely_pathogenic	0.7871	pathogenic	-1.373	Destabilizing	0.992	D	0.769	deleterious	None	None	None	None	I
P/Y	0.5129	ambiguous	0.5616	ambiguous	-1.105	Destabilizing	0.972	D	0.775	deleterious	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.