TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30565	91918;91919;91920	chr2:178550145;178550144;178550143	chr2:179414872;179414871;179414870
N2AB	28924	86995;86996;86997	chr2:178550145;178550144;178550143	chr2:179414872;179414871;179414870
N2A	27997	84214;84215;84216	chr2:178550145;178550144;178550143	chr2:179414872;179414871;179414870
N2B	21500	64723;64724;64725	chr2:178550145;178550144;178550143	chr2:179414872;179414871;179414870
Novex-1	21625	65098;65099;65100	chr2:178550145;178550144;178550143	chr2:179414872;179414871;179414870
Novex-2	21692	65299;65300;65301	chr2:178550145;178550144;178550143	chr2:179414872;179414871;179414870
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-149
• Domain position: 34
• Structural Position: 55
• Q(SASA): 0.3537
• 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
V/M	None	None	0.427	N	0.321	0.075	0.456462010053	gnomAD-4.0.0	1.59124E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02389E-05

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	0.0804	likely_benign	0.0883	benign	-0.639	Destabilizing	0.019	N	0.248	neutral	N	0.480185064	None	None	N
V/C	0.3878	ambiguous	0.4249	ambiguous	-0.736	Destabilizing	0.958	D	0.381	neutral	None	None	None	None	N
V/D	0.1295	likely_benign	0.1739	benign	-0.221	Destabilizing	0.055	N	0.369	neutral	None	None	None	None	N
V/E	0.098	likely_benign	0.125	benign	-0.29	Destabilizing	None	N	0.221	neutral	N	0.388197623	None	None	N
V/F	0.1087	likely_benign	0.1157	benign	-0.613	Destabilizing	0.497	N	0.427	neutral	None	None	None	None	N
V/G	0.1113	likely_benign	0.1237	benign	-0.82	Destabilizing	0.081	N	0.389	neutral	N	0.482649367	None	None	N
V/H	0.1999	likely_benign	0.2257	benign	-0.21	Destabilizing	0.497	N	0.431	neutral	None	None	None	None	N
V/I	0.0626	likely_benign	0.0602	benign	-0.292	Destabilizing	0.001	N	0.227	neutral	None	None	None	None	N
V/K	0.1002	likely_benign	0.1156	benign	-0.563	Destabilizing	None	N	0.191	neutral	None	None	None	None	N
V/L	0.0991	likely_benign	0.1017	benign	-0.292	Destabilizing	0.007	N	0.255	neutral	N	0.478704984	None	None	N
V/M	0.0745	likely_benign	0.0758	benign	-0.461	Destabilizing	0.427	N	0.321	neutral	N	0.49538659	None	None	N
V/N	0.0842	likely_benign	0.0928	benign	-0.409	Destabilizing	0.22	N	0.434	neutral	None	None	None	None	N
V/P	0.6353	likely_pathogenic	0.6963	pathogenic	-0.373	Destabilizing	0.364	N	0.426	neutral	None	None	None	None	N
V/Q	0.0993	likely_benign	0.1144	benign	-0.58	Destabilizing	None	N	0.215	neutral	None	None	None	None	N
V/R	0.1104	likely_benign	0.1255	benign	-0.058	Destabilizing	0.055	N	0.389	neutral	None	None	None	None	N
V/S	0.0878	likely_benign	0.0953	benign	-0.837	Destabilizing	0.055	N	0.336	neutral	None	None	None	None	N
V/T	0.0804	likely_benign	0.0842	benign	-0.796	Destabilizing	0.104	N	0.224	neutral	None	None	None	None	N
V/W	0.5201	ambiguous	0.5684	pathogenic	-0.709	Destabilizing	0.958	D	0.42	neutral	None	None	None	None	N
V/Y	0.2703	likely_benign	0.286	benign	-0.424	Destabilizing	0.667	D	0.436	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.