TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8544	25855;25856;25857	chr2:178717104;178717103;178717102	chr2:179581831;179581830;179581829
N2AB	8227	24904;24905;24906	chr2:178717104;178717103;178717102	chr2:179581831;179581830;179581829
N2A	7300	22123;22124;22125	chr2:178717104;178717103;178717102	chr2:179581831;179581830;179581829
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: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Ig-70
• Domain position: 89
• Structural Position: 175
• Q(SASA): 0.1643
• 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
G/A	rs2077603060	None	0.009	N	0.189	0.202	0.178374595973	gnomAD-4.0.0	1.3717E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80309E-06	0	0
G/D	None	None	0.861	N	0.631	0.257	0.312306559268	gnomAD-4.0.0	2.7434E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.60617E-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
G/A	0.0726	likely_benign	0.0707	benign	-0.648	Destabilizing	0.009	N	0.189	neutral	N	0.446707209	None	None	N
G/C	0.1857	likely_benign	0.1878	benign	-1.032	Destabilizing	0.998	D	0.622	neutral	N	0.506256945	None	None	N
G/D	0.186	likely_benign	0.1779	benign	-1.119	Destabilizing	0.861	D	0.631	neutral	N	0.439666594	None	None	N
G/E	0.1461	likely_benign	0.1421	benign	-1.185	Destabilizing	0.956	D	0.627	neutral	None	None	None	None	N
G/F	0.2981	likely_benign	0.2939	benign	-1.001	Destabilizing	0.994	D	0.681	prob.neutral	None	None	None	None	N
G/H	0.2096	likely_benign	0.2029	benign	-1.218	Destabilizing	0.999	D	0.581	neutral	None	None	None	None	N
G/I	0.1348	likely_benign	0.1345	benign	-0.298	Destabilizing	0.917	D	0.669	neutral	None	None	None	None	N
G/K	0.2155	likely_benign	0.2079	benign	-1.286	Destabilizing	0.956	D	0.622	neutral	None	None	None	None	N
G/L	0.1755	likely_benign	0.1739	benign	-0.298	Destabilizing	0.917	D	0.634	neutral	None	None	None	None	N
G/M	0.231	likely_benign	0.2265	benign	-0.327	Destabilizing	0.994	D	0.639	neutral	None	None	None	None	N
G/N	0.1799	likely_benign	0.1758	benign	-0.983	Destabilizing	0.987	D	0.605	neutral	None	None	None	None	N
G/P	0.8463	likely_pathogenic	0.8481	pathogenic	-0.373	Destabilizing	0.983	D	0.637	neutral	None	None	None	None	N
G/Q	0.185	likely_benign	0.1826	benign	-1.166	Destabilizing	0.994	D	0.659	neutral	None	None	None	None	N
G/R	0.1436	likely_benign	0.1407	benign	-0.937	Destabilizing	0.983	D	0.637	neutral	N	0.430604393	None	None	N
G/S	0.0777	likely_benign	0.0772	benign	-1.235	Destabilizing	0.037	N	0.401	neutral	N	0.387890979	None	None	N
G/T	0.0829	likely_benign	0.0816	benign	-1.215	Destabilizing	0.227	N	0.331	neutral	None	None	None	None	N
G/V	0.0956	likely_benign	0.0957	benign	-0.373	Destabilizing	0.182	N	0.391	neutral	N	0.408420967	None	None	N
G/W	0.2387	likely_benign	0.2379	benign	-1.344	Destabilizing	0.999	D	0.621	neutral	None	None	None	None	N
G/Y	0.2478	likely_benign	0.2416	benign	-0.927	Destabilizing	0.998	D	0.654	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.