TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5004	15235;15236;15237	chr2:178734914;178734913;178734912	chr2:179599641;179599640;179599639
N2AB	4687	14284;14285;14286	chr2:178734914;178734913;178734912	chr2:179599641;179599640;179599639
N2A	3760	11503;11504;11505	chr2:178734914;178734913;178734912	chr2:179599641;179599640;179599639
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-33
• Domain position: 24
• Structural Position: 34
• Q(SASA): 0.3712
• 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
K/E	None	None	0.027	N	0.434	0.202	0.278968121808	gnomAD-4.0.0	1.59415E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86269E-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	0.6207	likely_pathogenic	0.6756	pathogenic	-0.832	Destabilizing	0.035	N	0.479	neutral	None	None	None	None	N
K/C	0.8406	likely_pathogenic	0.8443	pathogenic	-0.929	Destabilizing	0.935	D	0.576	neutral	None	None	None	None	N
K/D	0.8996	likely_pathogenic	0.9265	pathogenic	-1.017	Destabilizing	0.149	N	0.485	neutral	None	None	None	None	N
K/E	0.4319	ambiguous	0.4815	ambiguous	-0.843	Destabilizing	0.027	N	0.434	neutral	N	0.503201079	None	None	N
K/F	0.8908	likely_pathogenic	0.8956	pathogenic	-0.249	Destabilizing	0.555	D	0.601	neutral	None	None	None	None	N
K/G	0.7996	likely_pathogenic	0.8375	pathogenic	-1.268	Destabilizing	0.149	N	0.547	neutral	None	None	None	None	N
K/H	0.4064	ambiguous	0.4491	ambiguous	-1.635	Destabilizing	0.555	D	0.582	neutral	None	None	None	None	N
K/I	0.4589	ambiguous	0.4792	ambiguous	0.341	Stabilizing	0.38	N	0.603	neutral	None	None	None	None	N
K/L	0.5291	ambiguous	0.5559	ambiguous	0.341	Stabilizing	0.149	N	0.543	neutral	None	None	None	None	N
K/M	0.3786	ambiguous	0.3946	ambiguous	0.22	Stabilizing	0.741	D	0.583	neutral	D	0.56227475	None	None	N
K/N	0.759	likely_pathogenic	0.7938	pathogenic	-1.251	Destabilizing	0.117	N	0.42	neutral	N	0.510271479	None	None	N
K/P	0.9487	likely_pathogenic	0.9703	pathogenic	-0.022	Destabilizing	0.555	D	0.59	neutral	None	None	None	None	N
K/Q	0.1809	likely_benign	0.198	benign	-1.166	Destabilizing	0.117	N	0.48	neutral	N	0.51082682	None	None	N
K/R	0.0891	likely_benign	0.0927	benign	-1.166	Destabilizing	None	N	0.255	neutral	N	0.480940289	None	None	N
K/S	0.6857	likely_pathogenic	0.7337	pathogenic	-1.788	Destabilizing	0.003	N	0.132	neutral	None	None	None	None	N
K/T	0.3109	likely_benign	0.3518	ambiguous	-1.393	Destabilizing	0.001	N	0.237	neutral	N	0.50802636	None	None	N
K/V	0.4338	ambiguous	0.4681	ambiguous	-0.022	Destabilizing	0.149	N	0.543	neutral	None	None	None	None	N
K/W	0.8693	likely_pathogenic	0.8739	pathogenic	-0.242	Destabilizing	0.935	D	0.591	neutral	None	None	None	None	N
K/Y	0.7922	likely_pathogenic	0.8014	pathogenic	0.07	Stabilizing	0.555	D	0.588	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.