TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6489	19690;19691;19692	chr2:178728359;178728358;178728357	chr2:179593086;179593085;179593084
N2AB	6172	18739;18740;18741	chr2:178728359;178728358;178728357	chr2:179593086;179593085;179593084
N2A	5245	15958;15959;15960	chr2:178728359;178728358;178728357	chr2:179593086;179593085;179593084
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: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-49
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.6908
• 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	0.134	N	0.116	0.078	0.1749357433	gnomAD-4.0.0	1.61465E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.47189E-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
K/A	0.2771	likely_benign	0.2872	benign	-0.093	Destabilizing	0.863	D	0.31	neutral	None	None	None	None	N
K/C	0.7965	likely_pathogenic	0.8218	pathogenic	-0.123	Destabilizing	0.999	D	0.393	neutral	None	None	None	None	N
K/D	0.4605	ambiguous	0.4801	ambiguous	0.053	Stabilizing	0.02	N	0.132	neutral	None	None	None	None	N
K/E	0.1659	likely_benign	0.1659	benign	0.08	Stabilizing	0.134	N	0.116	neutral	N	0.408299884	None	None	N
K/F	0.8114	likely_pathogenic	0.8373	pathogenic	-0.159	Destabilizing	0.997	D	0.381	neutral	None	None	None	None	N
K/G	0.4002	ambiguous	0.4071	ambiguous	-0.344	Destabilizing	0.969	D	0.317	neutral	None	None	None	None	N
K/H	0.36	ambiguous	0.3908	ambiguous	-0.686	Destabilizing	0.997	D	0.403	neutral	None	None	None	None	N
K/I	0.4334	ambiguous	0.4544	ambiguous	0.505	Stabilizing	0.996	D	0.388	neutral	N	0.456412903	None	None	N
K/L	0.4166	ambiguous	0.4391	ambiguous	0.505	Stabilizing	0.969	D	0.36	neutral	None	None	None	None	N
K/M	0.2776	likely_benign	0.2955	benign	0.347	Stabilizing	0.999	D	0.393	neutral	None	None	None	None	N
K/N	0.3432	ambiguous	0.3865	ambiguous	0.185	Stabilizing	0.92	D	0.311	neutral	N	0.42496006	None	None	N
K/P	0.4838	ambiguous	0.4914	ambiguous	0.335	Stabilizing	0.046	N	0.173	neutral	None	None	None	None	N
K/Q	0.1355	likely_benign	0.1419	benign	0.016	Stabilizing	0.92	D	0.381	neutral	N	0.480450771	None	None	N
K/R	0.0872	likely_benign	0.0856	benign	-0.138	Destabilizing	0.92	D	0.343	neutral	N	0.498689815	None	None	N
K/S	0.3319	likely_benign	0.3657	ambiguous	-0.335	Destabilizing	0.863	D	0.283	neutral	None	None	None	None	N
K/T	0.1606	likely_benign	0.1756	benign	-0.144	Destabilizing	0.959	D	0.329	neutral	N	0.4559764	None	None	N
K/V	0.3386	likely_benign	0.3562	ambiguous	0.335	Stabilizing	0.969	D	0.365	neutral	None	None	None	None	N
K/W	0.8201	likely_pathogenic	0.8334	pathogenic	-0.131	Destabilizing	0.999	D	0.517	neutral	None	None	None	None	N
K/Y	0.6776	likely_pathogenic	0.6909	pathogenic	0.199	Stabilizing	0.997	D	0.378	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.