TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25751	77476;77477;77478	chr2:178568881;178568880;178568879	chr2:179433608;179433607;179433606
N2AB	24110	72553;72554;72555	chr2:178568881;178568880;178568879	chr2:179433608;179433607;179433606
N2A	23183	69772;69773;69774	chr2:178568881;178568880;178568879	chr2:179433608;179433607;179433606
N2B	16686	50281;50282;50283	chr2:178568881;178568880;178568879	chr2:179433608;179433607;179433606
Novex-1	16811	50656;50657;50658	chr2:178568881;178568880;178568879	chr2:179433608;179433607;179433606
Novex-2	16878	50857;50858;50859	chr2:178568881;178568880;178568879	chr2:179433608;179433607;179433606
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-75
• Domain position: 54
• Structural Position: 77
• Q(SASA): 0.1969
• 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
V/I	rs1707037065	None	0.305	N	0.497	0.184	0.506189230309	gnomAD-4.0.0	1.59276E-06	None	None	None	None	I	None	0	0	None	0	2.77562E-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
V/A	0.3245	likely_benign	0.3165	benign	-1.472	Destabilizing	0.369	N	0.407	neutral	N	0.479153464	None	None	I
V/C	0.7602	likely_pathogenic	0.748	pathogenic	-0.882	Destabilizing	0.997	D	0.551	neutral	None	None	None	None	I
V/D	0.8017	likely_pathogenic	0.7889	pathogenic	-1.47	Destabilizing	0.97	D	0.566	neutral	None	None	None	None	I
V/E	0.6451	likely_pathogenic	0.6332	pathogenic	-1.334	Destabilizing	0.798	D	0.545	neutral	N	0.507448709	None	None	I
V/F	0.4534	ambiguous	0.4128	ambiguous	-0.823	Destabilizing	0.98	D	0.593	neutral	None	None	None	None	I
V/G	0.321	likely_benign	0.3203	benign	-1.925	Destabilizing	0.029	N	0.441	neutral	N	0.517190723	None	None	I
V/H	0.8868	likely_pathogenic	0.8782	pathogenic	-1.58	Destabilizing	0.998	D	0.643	neutral	None	None	None	None	I
V/I	0.141	likely_benign	0.1379	benign	-0.268	Destabilizing	0.305	N	0.497	neutral	N	0.517057437	None	None	I
V/K	0.8291	likely_pathogenic	0.8168	pathogenic	-1.178	Destabilizing	0.92	D	0.543	neutral	None	None	None	None	I
V/L	0.4797	ambiguous	0.4815	ambiguous	-0.268	Destabilizing	0.154	N	0.503	neutral	N	0.476635477	None	None	I
V/M	0.3492	ambiguous	0.3412	ambiguous	-0.233	Destabilizing	0.991	D	0.553	neutral	None	None	None	None	I
V/N	0.603	likely_pathogenic	0.5928	pathogenic	-1.245	Destabilizing	0.629	D	0.572	neutral	None	None	None	None	I
V/P	0.9631	likely_pathogenic	0.9578	pathogenic	-0.637	Destabilizing	0.775	D	0.58	neutral	None	None	None	None	I
V/Q	0.6676	likely_pathogenic	0.6505	pathogenic	-1.197	Destabilizing	0.89	D	0.612	neutral	None	None	None	None	I
V/R	0.8072	likely_pathogenic	0.8038	pathogenic	-0.935	Destabilizing	0.961	D	0.639	neutral	None	None	None	None	I
V/S	0.3406	ambiguous	0.3367	benign	-1.858	Destabilizing	0.048	N	0.398	neutral	None	None	None	None	I
V/T	0.2647	likely_benign	0.2736	benign	-1.59	Destabilizing	0.02	N	0.281	neutral	None	None	None	None	I
V/W	0.9746	likely_pathogenic	0.9709	pathogenic	-1.242	Destabilizing	0.999	D	0.698	prob.neutral	None	None	None	None	I
V/Y	0.8799	likely_pathogenic	0.8601	pathogenic	-0.829	Destabilizing	0.993	D	0.583	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.