TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6930	21013;21014;21015	chr2:178725416;178725415;178725414	chr2:179590143;179590142;179590141
N2AB	6613	20062;20063;20064	chr2:178725416;178725415;178725414	chr2:179590143;179590142;179590141
N2A	5686	17281;17282;17283	chr2:178725416;178725415;178725414	chr2:179590143;179590142;179590141
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: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-53
• Domain position: 77
• Structural Position: 159
• Q(SASA): 0.2638
• 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
K/E	None	None	0.042	N	0.274	0.148	0.264547087235	gnomAD-4.0.0	1.60563E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.88391E-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
K/A	0.5342	ambiguous	0.5024	ambiguous	-0.837	Destabilizing	0.055	N	0.429	neutral	None	None	None	None	I
K/C	0.7439	likely_pathogenic	0.7211	pathogenic	-0.875	Destabilizing	0.958	D	0.525	neutral	None	None	None	None	I
K/D	0.8431	likely_pathogenic	0.8249	pathogenic	-0.585	Destabilizing	0.22	N	0.411	neutral	None	None	None	None	I
K/E	0.2988	likely_benign	0.2589	benign	-0.423	Destabilizing	0.042	N	0.274	neutral	N	0.494327798	None	None	I
K/F	0.8598	likely_pathogenic	0.832	pathogenic	-0.362	Destabilizing	0.667	D	0.551	neutral	None	None	None	None	I
K/G	0.6097	likely_pathogenic	0.5754	pathogenic	-1.259	Destabilizing	0.124	N	0.474	neutral	None	None	None	None	I
K/H	0.3589	ambiguous	0.3298	benign	-1.61	Destabilizing	0.667	D	0.473	neutral	None	None	None	None	I
K/I	0.5137	ambiguous	0.484	ambiguous	0.288	Stabilizing	0.004	N	0.457	neutral	None	None	None	None	I
K/L	0.5571	ambiguous	0.5286	ambiguous	0.288	Stabilizing	0.055	N	0.483	neutral	None	None	None	None	I
K/M	0.3484	ambiguous	0.3279	benign	0.184	Stabilizing	0.602	D	0.481	neutral	N	0.510232727	None	None	I
K/N	0.6468	likely_pathogenic	0.6021	pathogenic	-0.889	Destabilizing	0.175	N	0.287	neutral	N	0.491114514	None	None	I
K/P	0.9767	likely_pathogenic	0.9765	pathogenic	-0.058	Destabilizing	0.667	D	0.471	neutral	None	None	None	None	I
K/Q	0.1364	likely_benign	0.1233	benign	-0.875	Destabilizing	0.175	N	0.411	neutral	N	0.490354046	None	None	I
K/R	0.0754	likely_benign	0.0721	benign	-0.881	Destabilizing	None	N	0.113	neutral	D	0.534406338	None	None	I
K/S	0.5058	ambiguous	0.4619	ambiguous	-1.545	Destabilizing	0.002	N	0.123	neutral	None	None	None	None	I
K/T	0.2359	likely_benign	0.2143	benign	-1.155	Destabilizing	0.001	N	0.235	neutral	N	0.494461084	None	None	I
K/V	0.4982	ambiguous	0.4587	ambiguous	-0.058	Destabilizing	0.055	N	0.466	neutral	None	None	None	None	I
K/W	0.7566	likely_pathogenic	0.7379	pathogenic	-0.262	Destabilizing	0.958	D	0.576	neutral	None	None	None	None	I
K/Y	0.7323	likely_pathogenic	0.6916	pathogenic	0.047	Stabilizing	0.667	D	0.524	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.