TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7248	21967;21968;21969	chr2:178723265;178723264;178723263	chr2:179587992;179587991;179587990
N2AB	6931	21016;21017;21018	chr2:178723265;178723264;178723263	chr2:179587992;179587991;179587990
N2A	6004	18235;18236;18237	chr2:178723265;178723264;178723263	chr2:179587992;179587991;179587990
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-57
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.5707
• 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
I/T	None	None	0.007	N	0.353	0.183	0.334161072951	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
I/A	0.3783	ambiguous	0.5562	ambiguous	-1.502	Destabilizing	0.129	N	0.453	neutral	None	None	None	None	N
I/C	0.664	likely_pathogenic	0.7637	pathogenic	-0.831	Destabilizing	0.983	D	0.559	neutral	None	None	None	None	N
I/D	0.767	likely_pathogenic	0.8666	pathogenic	-1.047	Destabilizing	0.836	D	0.589	neutral	None	None	None	None	N
I/E	0.6187	likely_pathogenic	0.7672	pathogenic	-1.047	Destabilizing	0.418	N	0.534	neutral	None	None	None	None	N
I/F	0.1291	likely_benign	0.1827	benign	-1.005	Destabilizing	0.655	D	0.539	neutral	N	0.463338663	None	None	N
I/G	0.6864	likely_pathogenic	0.8266	pathogenic	-1.814	Destabilizing	0.593	D	0.539	neutral	None	None	None	None	N
I/H	0.4013	ambiguous	0.5384	ambiguous	-0.993	Destabilizing	0.983	D	0.571	neutral	None	None	None	None	N
I/K	0.3379	likely_benign	0.4996	ambiguous	-1.109	Destabilizing	0.01	N	0.471	neutral	None	None	None	None	N
I/L	0.0984	likely_benign	0.1432	benign	-0.721	Destabilizing	0.047	N	0.368	neutral	N	0.475543596	None	None	N
I/M	0.1104	likely_benign	0.1538	benign	-0.579	Destabilizing	0.047	N	0.386	neutral	N	0.508618807	None	None	N
I/N	0.3118	likely_benign	0.4463	ambiguous	-0.868	Destabilizing	0.794	D	0.595	neutral	N	0.487896818	None	None	N
I/P	0.8917	likely_pathogenic	0.9288	pathogenic	-0.951	Destabilizing	0.94	D	0.595	neutral	None	None	None	None	N
I/Q	0.41	ambiguous	0.5684	pathogenic	-1.037	Destabilizing	0.716	D	0.604	neutral	None	None	None	None	N
I/R	0.2395	likely_benign	0.3702	ambiguous	-0.499	Destabilizing	0.557	D	0.589	neutral	None	None	None	None	N
I/S	0.3043	likely_benign	0.4395	ambiguous	-1.422	Destabilizing	0.213	N	0.54	neutral	N	0.468790982	None	None	N
I/T	0.1951	likely_benign	0.2967	benign	-1.307	Destabilizing	0.007	N	0.353	neutral	N	0.400659048	None	None	N
I/V	0.0711	likely_benign	0.0907	benign	-0.951	Destabilizing	0.001	N	0.287	neutral	N	0.417303369	None	None	N
I/W	0.7214	likely_pathogenic	0.8001	pathogenic	-1.073	Destabilizing	0.983	D	0.594	neutral	None	None	None	None	N
I/Y	0.4156	ambiguous	0.5087	ambiguous	-0.873	Destabilizing	0.836	D	0.587	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.