TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6618	20077;20078;20079	chr2:178727726;178727725;178727724	chr2:179592453;179592452;179592451
N2AB	6301	19126;19127;19128	chr2:178727726;178727725;178727724	chr2:179592453;179592452;179592451
N2A	5374	16345;16346;16347	chr2:178727726;178727725;178727724	chr2:179592453;179592452;179592451
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: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-50
• Domain position: 45
• Structural Position: 102
• Q(SASA): 0.8861
• 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
P/A	None	None	0.811	N	0.403	0.119	0.178374595973	gnomAD-4.0.0	1.36878E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.31949E-05	0
P/L	None	None	0.938	N	0.491	0.291	0.512595481341	gnomAD-4.0.0	3.18465E-06	None	None	None	None	N	None	5.66765E-05	0	None	0	0	None	0	0	2.86074E-06	0	0
P/S	rs1234787097	-0.242	0.811	N	0.357	0.115	0.167679373172	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.56E-05	None	0	None	0	0	0
P/S	rs1234787097	-0.242	0.811	N	0.357	0.115	0.167679373172	gnomAD-4.0.0	6.84391E-07	None	None	None	None	N	None	0	0	None	0	2.52016E-05	None	0	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
P/A	0.0926	likely_benign	0.0977	benign	-0.348	Destabilizing	0.811	D	0.403	neutral	N	0.481624206	None	None	N
P/C	0.5793	likely_pathogenic	0.6732	pathogenic	-0.813	Destabilizing	0.999	D	0.597	neutral	None	None	None	None	N
P/D	0.3391	likely_benign	0.411	ambiguous	-0.243	Destabilizing	0.976	D	0.365	neutral	None	None	None	None	N
P/E	0.2259	likely_benign	0.2741	benign	-0.345	Destabilizing	0.976	D	0.367	neutral	None	None	None	None	N
P/F	0.5024	ambiguous	0.5561	ambiguous	-0.671	Destabilizing	0.997	D	0.554	neutral	None	None	None	None	N
P/G	0.2493	likely_benign	0.2813	benign	-0.412	Destabilizing	0.034	N	0.315	neutral	None	None	None	None	N
P/H	0.1985	likely_benign	0.2271	benign	0.041	Stabilizing	0.999	D	0.513	neutral	N	0.457075266	None	None	N
P/I	0.369	ambiguous	0.4028	ambiguous	-0.311	Destabilizing	0.976	D	0.555	neutral	None	None	None	None	N
P/K	0.2578	likely_benign	0.3043	benign	-0.372	Destabilizing	0.976	D	0.371	neutral	None	None	None	None	N
P/L	0.1489	likely_benign	0.1616	benign	-0.311	Destabilizing	0.938	D	0.491	neutral	N	0.475834385	None	None	N
P/M	0.3206	likely_benign	0.3627	ambiguous	-0.62	Destabilizing	0.999	D	0.512	neutral	None	None	None	None	N
P/N	0.2682	likely_benign	0.2966	benign	-0.195	Destabilizing	0.976	D	0.491	neutral	None	None	None	None	N
P/Q	0.1367	likely_benign	0.1504	benign	-0.371	Destabilizing	0.988	D	0.369	neutral	None	None	None	None	N
P/R	0.1849	likely_benign	0.2138	benign	0.042	Stabilizing	0.984	D	0.483	neutral	N	0.425770924	None	None	N
P/S	0.1123	likely_benign	0.1187	benign	-0.528	Destabilizing	0.811	D	0.357	neutral	N	0.452666736	None	None	N
P/T	0.1081	likely_benign	0.117	benign	-0.537	Destabilizing	0.103	N	0.304	neutral	N	0.449282502	None	None	N
P/V	0.2592	likely_benign	0.2862	benign	-0.296	Destabilizing	0.952	D	0.41	neutral	None	None	None	None	N
P/W	0.6103	likely_pathogenic	0.6887	pathogenic	-0.725	Destabilizing	0.999	D	0.628	neutral	None	None	None	None	N
P/Y	0.4392	ambiguous	0.5142	ambiguous	-0.462	Destabilizing	0.999	D	0.554	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.