TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21250	63973;63974;63975	chr2:178587561;178587560;178587559	chr2:179452288;179452287;179452286
N2AB	19609	59050;59051;59052	chr2:178587561;178587560;178587559	chr2:179452288;179452287;179452286
N2A	18682	56269;56270;56271	chr2:178587561;178587560;178587559	chr2:179452288;179452287;179452286
N2B	12185	36778;36779;36780	chr2:178587561;178587560;178587559	chr2:179452288;179452287;179452286
Novex-1	12310	37153;37154;37155	chr2:178587561;178587560;178587559	chr2:179452288;179452287;179452286
Novex-2	12377	37354;37355;37356	chr2:178587561;178587560;178587559	chr2:179452288;179452287;179452286
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-123
• Domain position: 74
• Structural Position: 161
• Q(SASA): 0.2159
• 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
N/K	rs773738001	-0.404	1.0	D	0.717	0.541	0.336155897331	gnomAD-2.1.1	8.11E-06	None	None	None	None	I	None	0	0	None	0	1.13289E-04	None	0	None	0	0	0
N/K	rs773738001	-0.404	1.0	D	0.717	0.541	0.336155897331	gnomAD-4.0.0	3.19096E-06	None	None	None	None	I	None	0	0	None	0	5.58534E-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
N/A	0.9638	likely_pathogenic	0.9669	pathogenic	-0.699	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
N/C	0.7771	likely_pathogenic	0.8135	pathogenic	0.098	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
N/D	0.9744	likely_pathogenic	0.9716	pathogenic	-0.836	Destabilizing	0.999	D	0.602	neutral	D	0.535635958	None	None	I
N/E	0.9942	likely_pathogenic	0.9943	pathogenic	-0.791	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	I
N/F	0.9958	likely_pathogenic	0.9961	pathogenic	-0.69	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	I
N/G	0.9072	likely_pathogenic	0.9089	pathogenic	-0.988	Destabilizing	0.999	D	0.55	neutral	None	None	None	None	I
N/H	0.8848	likely_pathogenic	0.8905	pathogenic	-0.986	Destabilizing	1.0	D	0.735	prob.delet.	D	0.543651355	None	None	I
N/I	0.9677	likely_pathogenic	0.9677	pathogenic	0.012	Stabilizing	1.0	D	0.731	prob.delet.	D	0.532548539	None	None	I
N/K	0.9969	likely_pathogenic	0.997	pathogenic	-0.327	Destabilizing	1.0	D	0.717	prob.delet.	D	0.554500681	None	None	I
N/L	0.9223	likely_pathogenic	0.9251	pathogenic	0.012	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
N/M	0.9684	likely_pathogenic	0.9695	pathogenic	0.6	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
N/P	0.99	likely_pathogenic	0.9896	pathogenic	-0.196	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
N/Q	0.9917	likely_pathogenic	0.9923	pathogenic	-0.983	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
N/R	0.9959	likely_pathogenic	0.9959	pathogenic	-0.304	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
N/S	0.3412	ambiguous	0.3362	benign	-0.767	Destabilizing	0.999	D	0.568	neutral	N	0.478992561	None	None	I
N/T	0.7896	likely_pathogenic	0.7847	pathogenic	-0.56	Destabilizing	0.999	D	0.689	prob.neutral	D	0.535889447	None	None	I
N/V	0.9668	likely_pathogenic	0.9704	pathogenic	-0.196	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
N/W	0.9991	likely_pathogenic	0.9992	pathogenic	-0.53	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	I
N/Y	0.9771	likely_pathogenic	0.9775	pathogenic	-0.302	Destabilizing	1.0	D	0.749	deleterious	D	0.55500766	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.