TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23224	69895;69896;69897	chr2:178576574;178576573;178576572	chr2:179441301;179441300;179441299
N2AB	21583	64972;64973;64974	chr2:178576574;178576573;178576572	chr2:179441301;179441300;179441299
N2A	20656	62191;62192;62193	chr2:178576574;178576573;178576572	chr2:179441301;179441300;179441299
N2B	14159	42700;42701;42702	chr2:178576574;178576573;178576572	chr2:179441301;179441300;179441299
Novex-1	14284	43075;43076;43077	chr2:178576574;178576573;178576572	chr2:179441301;179441300;179441299
Novex-2	14351	43276;43277;43278	chr2:178576574;178576573;178576572	chr2:179441301;179441300;179441299
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-56
• Domain position: 86
• Structural Position: 119
• Q(SASA): 0.5174
• Predicted PPI site: I

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/L	rs762758398	-0.318	0.007	N	0.419	0.209	0.429203605099	gnomAD-2.1.1	8.06E-06	None	None	None	None	I	None	0	2.9E-05	None	0	5.58E-05	None	0	None	0	0	0
P/L	rs762758398	-0.318	0.007	N	0.419	0.209	0.429203605099	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/L	rs762758398	-0.318	0.007	N	0.419	0.209	0.429203605099	gnomAD-4.0.0	3.0989E-06	None	None	None	None	I	None	0	3.33378E-05	None	0	0	None	0	0	2.54313E-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
P/A	0.0776	likely_benign	0.0784	benign	-1.113	Destabilizing	0.472	N	0.446	neutral	N	0.438098008	None	None	I
P/C	0.3726	ambiguous	0.3905	ambiguous	-0.769	Destabilizing	0.996	D	0.519	neutral	None	None	None	None	I
P/D	0.3589	ambiguous	0.3752	ambiguous	-0.908	Destabilizing	0.009	N	0.251	neutral	None	None	None	None	I
P/E	0.1826	likely_benign	0.1881	benign	-0.995	Destabilizing	0.005	N	0.198	neutral	None	None	None	None	I
P/F	0.3054	likely_benign	0.3127	benign	-1.124	Destabilizing	0.91	D	0.51	neutral	None	None	None	None	I
P/G	0.2939	likely_benign	0.2917	benign	-1.317	Destabilizing	0.742	D	0.502	neutral	None	None	None	None	I
P/H	0.1657	likely_benign	0.1746	benign	-0.815	Destabilizing	0.984	D	0.497	neutral	None	None	None	None	I
P/I	0.1723	likely_benign	0.1743	benign	-0.695	Destabilizing	0.835	D	0.539	neutral	None	None	None	None	I
P/K	0.1736	likely_benign	0.1931	benign	-0.86	Destabilizing	0.742	D	0.449	neutral	None	None	None	None	I
P/L	0.0776	likely_benign	0.0797	benign	-0.695	Destabilizing	0.007	N	0.419	neutral	N	0.462745736	None	None	I
P/M	0.182	likely_benign	0.1842	benign	-0.475	Destabilizing	0.91	D	0.495	neutral	None	None	None	None	I
P/N	0.2665	likely_benign	0.276	benign	-0.563	Destabilizing	0.59	D	0.543	neutral	None	None	None	None	I
P/Q	0.1158	likely_benign	0.1217	benign	-0.86	Destabilizing	0.684	D	0.564	neutral	N	0.449853797	None	None	I
P/R	0.1493	likely_benign	0.1657	benign	-0.244	Destabilizing	0.884	D	0.527	neutral	N	0.468882275	None	None	I
P/S	0.1212	likely_benign	0.1227	benign	-0.987	Destabilizing	0.684	D	0.443	neutral	N	0.487814752	None	None	I
P/T	0.1026	likely_benign	0.1046	benign	-0.979	Destabilizing	0.684	D	0.483	neutral	N	0.473538733	None	None	I
P/V	0.1256	likely_benign	0.1278	benign	-0.799	Destabilizing	0.59	D	0.509	neutral	None	None	None	None	I
P/W	0.5024	ambiguous	0.5274	ambiguous	-1.183	Destabilizing	0.996	D	0.613	neutral	None	None	None	None	I
P/Y	0.2998	likely_benign	0.3137	benign	-0.916	Destabilizing	0.953	D	0.503	neutral	None	None	None	None	I

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.