TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14511	43756;43757;43758	chr2:178632363;178632362;178632361	chr2:179497090;179497089;179497088
N2AB	12870	38833;38834;38835	chr2:178632363;178632362;178632361	chr2:179497090;179497089;179497088
N2A	11943	36052;36053;36054	chr2:178632363;178632362;178632361	chr2:179497090;179497089;179497088
N2B	5446	16561;16562;16563	chr2:178632363;178632362;178632361	chr2:179497090;179497089;179497088
Novex-1	5571	16936;16937;16938	chr2:178632363;178632362;178632361	chr2:179497090;179497089;179497088
Novex-2	5638	17137;17138;17139	chr2:178632363;178632362;178632361	chr2:179497090;179497089;179497088
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-96
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.816
• 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/N	None	None	0.024	N	0.34	0.115	0.163833314356	gnomAD-4.0.0	1.6151E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.89645E-05	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
K/A	0.4098	ambiguous	0.3676	ambiguous	0.017	Stabilizing	0.014	N	0.432	neutral	None	None	None	None	N
K/C	0.7166	likely_pathogenic	0.6531	pathogenic	-0.162	Destabilizing	0.864	D	0.486	neutral	None	None	None	None	N
K/D	0.5701	likely_pathogenic	0.5296	ambiguous	-0.01	Destabilizing	0.072	N	0.429	neutral	None	None	None	None	N
K/E	0.1758	likely_benign	0.1574	benign	None	Stabilizing	0.005	N	0.339	neutral	N	0.496110537	None	None	N
K/F	0.8048	likely_pathogenic	0.7591	pathogenic	-0.126	Destabilizing	0.356	N	0.5	neutral	None	None	None	None	N
K/G	0.2207	likely_benign	0.1922	benign	-0.196	Destabilizing	0.031	N	0.43	neutral	None	None	None	None	N
K/H	0.3266	likely_benign	0.2666	benign	-0.437	Destabilizing	0.356	N	0.486	neutral	None	None	None	None	N
K/I	0.5486	ambiguous	0.4983	ambiguous	0.502	Stabilizing	0.356	N	0.505	neutral	None	None	None	None	N
K/L	0.4099	ambiguous	0.3625	ambiguous	0.502	Stabilizing	0.031	N	0.43	neutral	None	None	None	None	N
K/M	0.2617	likely_benign	0.243	benign	0.254	Stabilizing	0.56	D	0.496	neutral	N	0.510047206	None	None	N
K/N	0.331	likely_benign	0.3033	benign	0.225	Stabilizing	0.024	N	0.34	neutral	N	0.489183726	None	None	N
K/P	0.9006	likely_pathogenic	0.8782	pathogenic	0.369	Stabilizing	0.136	N	0.485	neutral	None	None	None	None	N
K/Q	0.1291	likely_benign	0.1081	benign	0.049	Stabilizing	None	N	0.213	neutral	N	0.464060589	None	None	N
K/R	0.0591	likely_benign	0.0542	benign	-0.053	Destabilizing	None	N	0.173	neutral	N	0.388318887	None	None	N
K/S	0.4496	ambiguous	0.3927	ambiguous	-0.246	Destabilizing	0.031	N	0.372	neutral	None	None	None	None	N
K/T	0.2355	likely_benign	0.2108	benign	-0.089	Destabilizing	0.024	N	0.42	neutral	N	0.490848369	None	None	N
K/V	0.5287	ambiguous	0.4884	ambiguous	0.369	Stabilizing	0.072	N	0.473	neutral	None	None	None	None	N
K/W	0.6513	likely_pathogenic	0.5406	ambiguous	-0.138	Destabilizing	0.864	D	0.489	neutral	None	None	None	None	N
K/Y	0.6368	likely_pathogenic	0.578	pathogenic	0.199	Stabilizing	0.356	N	0.478	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.