TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5638	17137;17138;17139	chr2:178731963;178731962;178731961	chr2:179596690;179596689;179596688
N2AB	5321	16186;16187;16188	chr2:178731963;178731962;178731961	chr2:179596690;179596689;179596688
N2A	4394	13405;13406;13407	chr2:178731963;178731962;178731961	chr2:179596690;179596689;179596688
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: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-40
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.5917
• 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
Y/N	rs777950405	-0.192	0.642	N	0.458	0.259	0.405560941015	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.34E-05	None	0	0	0
Y/N	rs777950405	-0.192	0.642	N	0.458	0.259	0.405560941015	gnomAD-4.0.0	1.61146E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.44504E-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
Y/A	0.2102	likely_benign	0.2219	benign	-1.104	Destabilizing	0.176	N	0.282	neutral	None	None	None	None	N
Y/C	0.0788	likely_benign	0.0854	benign	-0.26	Destabilizing	0.013	N	0.291	neutral	N	0.489017978	None	None	N
Y/D	0.164	likely_benign	0.1657	benign	0.674	Stabilizing	0.473	N	0.441	neutral	N	0.48033978	None	None	N
Y/E	0.3307	likely_benign	0.3364	benign	0.703	Stabilizing	0.031	N	0.311	neutral	None	None	None	None	N
Y/F	0.0824	likely_benign	0.0805	benign	-0.335	Destabilizing	0.784	D	0.394	neutral	N	0.465949118	None	None	N
Y/G	0.2508	likely_benign	0.2554	benign	-1.339	Destabilizing	0.495	N	0.405	neutral	None	None	None	None	N
Y/H	0.0887	likely_benign	0.0966	benign	0.08	Stabilizing	0.975	D	0.456	neutral	N	0.462100736	None	None	N
Y/I	0.1841	likely_benign	0.1951	benign	-0.464	Destabilizing	0.704	D	0.501	neutral	None	None	None	None	N
Y/K	0.3001	likely_benign	0.3264	benign	-0.219	Destabilizing	0.704	D	0.429	neutral	None	None	None	None	N
Y/L	0.2508	likely_benign	0.2696	benign	-0.464	Destabilizing	0.329	N	0.369	neutral	None	None	None	None	N
Y/M	0.3925	ambiguous	0.4027	ambiguous	-0.385	Destabilizing	0.981	D	0.437	neutral	None	None	None	None	N
Y/N	0.1109	likely_benign	0.114	benign	-0.546	Destabilizing	0.642	D	0.458	neutral	N	0.453134536	None	None	N
Y/P	0.8837	likely_pathogenic	0.8902	pathogenic	-0.662	Destabilizing	0.944	D	0.507	neutral	None	None	None	None	N
Y/Q	0.216	likely_benign	0.2304	benign	-0.436	Destabilizing	0.704	D	0.493	neutral	None	None	None	None	N
Y/R	0.1607	likely_benign	0.1771	benign	0.071	Stabilizing	0.704	D	0.517	neutral	None	None	None	None	N
Y/S	0.0898	likely_benign	0.0938	benign	-1.036	Destabilizing	0.029	N	0.277	neutral	N	0.374423036	None	None	N
Y/T	0.1549	likely_benign	0.1716	benign	-0.915	Destabilizing	0.031	N	0.298	neutral	None	None	None	None	N
Y/V	0.1405	likely_benign	0.1513	benign	-0.662	Destabilizing	0.329	N	0.402	neutral	None	None	None	None	N
Y/W	0.3381	likely_benign	0.3327	benign	-0.246	Destabilizing	0.995	D	0.459	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.