TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28264	85015;85016;85017	chr2:178561342;178561341;178561340	chr2:179426069;179426068;179426067
N2AB	26623	80092;80093;80094	chr2:178561342;178561341;178561340	chr2:179426069;179426068;179426067
N2A	25696	77311;77312;77313	chr2:178561342;178561341;178561340	chr2:179426069;179426068;179426067
N2B	19199	57820;57821;57822	chr2:178561342;178561341;178561340	chr2:179426069;179426068;179426067
Novex-1	19324	58195;58196;58197	chr2:178561342;178561341;178561340	chr2:179426069;179426068;179426067
Novex-2	19391	58396;58397;58398	chr2:178561342;178561341;178561340	chr2:179426069;179426068;179426067
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-94
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.1837
• 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/N	None	None	0.967	N	0.675	0.491	0.820480598388	gnomAD-4.0.0	1.59116E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-05	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	0.7352	likely_pathogenic	0.7437	pathogenic	-1.945	Destabilizing	0.845	D	0.482	neutral	None	None	None	None	N
I/C	0.8203	likely_pathogenic	0.8248	pathogenic	-1.962	Destabilizing	0.999	D	0.518	neutral	None	None	None	None	N
I/D	0.9681	likely_pathogenic	0.9677	pathogenic	-2.369	Highly Destabilizing	0.975	D	0.663	neutral	None	None	None	None	N
I/E	0.9219	likely_pathogenic	0.9158	pathogenic	-2.326	Highly Destabilizing	0.975	D	0.663	neutral	None	None	None	None	N
I/F	0.456	ambiguous	0.4557	ambiguous	-1.557	Destabilizing	0.983	D	0.451	neutral	N	0.486300397	None	None	N
I/G	0.9348	likely_pathogenic	0.9347	pathogenic	-2.286	Highly Destabilizing	0.975	D	0.637	neutral	None	None	None	None	N
I/H	0.8618	likely_pathogenic	0.8639	pathogenic	-1.546	Destabilizing	0.999	D	0.666	neutral	None	None	None	None	N
I/K	0.7216	likely_pathogenic	0.7083	pathogenic	-1.434	Destabilizing	0.975	D	0.664	neutral	None	None	None	None	N
I/L	0.2988	likely_benign	0.307	benign	-1.044	Destabilizing	0.63	D	0.332	neutral	N	0.520444458	None	None	N
I/M	0.221	likely_benign	0.2305	benign	-1.134	Destabilizing	0.994	D	0.443	neutral	N	0.500681669	None	None	N
I/N	0.7303	likely_pathogenic	0.7382	pathogenic	-1.512	Destabilizing	0.967	D	0.675	neutral	N	0.518025455	None	None	N
I/P	0.9713	likely_pathogenic	0.9678	pathogenic	-1.318	Destabilizing	0.987	D	0.679	prob.neutral	None	None	None	None	N
I/Q	0.8315	likely_pathogenic	0.8244	pathogenic	-1.719	Destabilizing	0.987	D	0.681	prob.neutral	None	None	None	None	N
I/R	0.642	likely_pathogenic	0.6244	pathogenic	-0.886	Destabilizing	0.975	D	0.681	prob.neutral	None	None	None	None	N
I/S	0.6875	likely_pathogenic	0.6971	pathogenic	-2.1	Highly Destabilizing	0.805	D	0.524	neutral	N	0.476639158	None	None	N
I/T	0.474	ambiguous	0.4855	ambiguous	-1.936	Destabilizing	0.025	N	0.251	neutral	N	0.471016844	None	None	N
I/V	0.0932	likely_benign	0.0916	benign	-1.318	Destabilizing	0.426	N	0.345	neutral	N	0.413602208	None	None	N
I/W	0.9469	likely_pathogenic	0.9503	pathogenic	-1.673	Destabilizing	0.999	D	0.692	prob.neutral	None	None	None	None	N
I/Y	0.8217	likely_pathogenic	0.8158	pathogenic	-1.384	Destabilizing	0.996	D	0.53	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.