TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3195	9808;9809;9810	chr2:178766501;178766500;178766499	chr2:179631228;179631227;179631226
N2AB	3195	9808;9809;9810	chr2:178766501;178766500;178766499	chr2:179631228;179631227;179631226
N2A	3195	9808;9809;9810	chr2:178766501;178766500;178766499	chr2:179631228;179631227;179631226
N2B	3149	9670;9671;9672	chr2:178766501;178766500;178766499	chr2:179631228;179631227;179631226
Novex-1	3149	9670;9671;9672	chr2:178766501;178766500;178766499	chr2:179631228;179631227;179631226
Novex-2	3149	9670;9671;9672	chr2:178766501;178766500;178766499	chr2:179631228;179631227;179631226
Novex-3	3195	9808;9809;9810	chr2:178766501;178766500;178766499	chr2:179631228;179631227;179631226

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-22
• Domain position: 49
• Structural Position: 122
• Q(SASA): 0.34
• 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	None	N	0.133	0.142	0.220303561663	gnomAD-4.0.0	1.59055E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85656E-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	0.2716	likely_benign	0.3088	benign	-0.848	Destabilizing	0.007	N	0.289	neutral	None	None	None	None	N
K/C	0.587	likely_pathogenic	0.6101	pathogenic	-0.871	Destabilizing	0.864	D	0.487	neutral	None	None	None	None	N
K/D	0.4702	ambiguous	0.5379	ambiguous	0.166	Stabilizing	0.016	N	0.345	neutral	None	None	None	None	N
K/E	0.1125	likely_benign	0.1399	benign	0.321	Stabilizing	None	N	0.133	neutral	N	0.513380518	None	None	N
K/F	0.7348	likely_pathogenic	0.8163	pathogenic	-0.556	Destabilizing	0.356	N	0.522	neutral	None	None	None	None	N
K/G	0.4181	ambiguous	0.4942	ambiguous	-1.202	Destabilizing	0.016	N	0.321	neutral	None	None	None	None	N
K/H	0.1702	likely_benign	0.1754	benign	-1.185	Destabilizing	None	N	0.275	neutral	None	None	None	None	N
K/I	0.2961	likely_benign	0.3687	ambiguous	0.079	Stabilizing	0.295	N	0.558	neutral	N	0.516047351	None	None	N
K/L	0.2888	likely_benign	0.3524	ambiguous	0.079	Stabilizing	0.031	N	0.426	neutral	None	None	None	None	N
K/M	0.2119	likely_benign	0.2577	benign	-0.236	Destabilizing	0.356	N	0.474	neutral	None	None	None	None	N
K/N	0.2527	likely_benign	0.2781	benign	-0.532	Destabilizing	None	N	0.122	neutral	N	0.481900073	None	None	N
K/P	0.9105	likely_pathogenic	0.9389	pathogenic	-0.203	Destabilizing	0.136	N	0.467	neutral	None	None	None	None	N
K/Q	0.0656	likely_benign	0.0626	benign	-0.477	Destabilizing	None	N	0.145	neutral	N	0.496956759	None	None	N
K/R	0.0858	likely_benign	0.0925	benign	-0.281	Destabilizing	0.012	N	0.307	neutral	N	0.493666121	None	None	N
K/S	0.2666	likely_benign	0.2828	benign	-1.287	Destabilizing	None	N	0.115	neutral	None	None	None	None	N
K/T	0.1049	likely_benign	0.1136	benign	-0.904	Destabilizing	0.012	N	0.386	neutral	N	0.502492763	None	None	N
K/V	0.2856	likely_benign	0.3293	benign	-0.203	Destabilizing	0.072	N	0.468	neutral	None	None	None	None	N
K/W	0.7157	likely_pathogenic	0.7869	pathogenic	-0.408	Destabilizing	0.864	D	0.494	neutral	None	None	None	None	N
K/Y	0.5174	ambiguous	0.5884	pathogenic	-0.125	Destabilizing	0.038	N	0.557	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.