TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18335	55228;55229;55230	chr2:178602399;178602398;178602397	chr2:179467126;179467125;179467124
N2AB	16694	50305;50306;50307	chr2:178602399;178602398;178602397	chr2:179467126;179467125;179467124
N2A	15767	47524;47525;47526	chr2:178602399;178602398;178602397	chr2:179467126;179467125;179467124
N2B	9270	28033;28034;28035	chr2:178602399;178602398;178602397	chr2:179467126;179467125;179467124
Novex-1	9395	28408;28409;28410	chr2:178602399;178602398;178602397	chr2:179467126;179467125;179467124
Novex-2	9462	28609;28610;28611	chr2:178602399;178602398;178602397	chr2:179467126;179467125;179467124
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: Fn3-21
• Domain position: 64
• Structural Position: 92
• Q(SASA): 0.3998
• 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/A	None	None	0.91	N	0.439	0.162	0.52437609879	gnomAD-4.0.0	1.59337E-06	None	None	None	None	N	None	5.67279E-05	0	None	0	0	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	0.1727	likely_benign	0.1555	benign	-0.576	Destabilizing	0.91	D	0.439	neutral	N	0.449467008	None	None	N
V/C	0.6772	likely_pathogenic	0.6571	pathogenic	-0.706	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
V/D	0.2957	likely_benign	0.2699	benign	-0.333	Destabilizing	0.996	D	0.714	prob.delet.	None	None	None	None	N
V/E	0.2259	likely_benign	0.2013	benign	-0.438	Destabilizing	0.994	D	0.674	neutral	N	0.446445345	None	None	N
V/F	0.1642	likely_benign	0.174	benign	-0.736	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	N
V/G	0.2637	likely_benign	0.2609	benign	-0.727	Destabilizing	0.98	D	0.672	neutral	N	0.481040708	None	None	N
V/H	0.4342	ambiguous	0.4203	ambiguous	-0.292	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
V/I	0.0734	likely_benign	0.0725	benign	-0.324	Destabilizing	0.931	D	0.526	neutral	None	None	None	None	N
V/K	0.2612	likely_benign	0.2523	benign	-0.557	Destabilizing	0.991	D	0.677	prob.neutral	None	None	None	None	N
V/L	0.1648	likely_benign	0.1556	benign	-0.324	Destabilizing	0.91	D	0.466	neutral	N	0.434209554	None	None	N
V/M	0.1274	likely_benign	0.1206	benign	-0.366	Destabilizing	0.998	D	0.572	neutral	N	0.480347275	None	None	N
V/N	0.208	likely_benign	0.19	benign	-0.308	Destabilizing	0.996	D	0.751	deleterious	None	None	None	None	N
V/P	0.6219	likely_pathogenic	0.542	ambiguous	-0.373	Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
V/Q	0.255	likely_benign	0.2367	benign	-0.541	Destabilizing	0.999	D	0.744	deleterious	None	None	None	None	N
V/R	0.2441	likely_benign	0.2354	benign	-0.033	Destabilizing	0.996	D	0.755	deleterious	None	None	None	None	N
V/S	0.181	likely_benign	0.168	benign	-0.691	Destabilizing	0.942	D	0.602	neutral	None	None	None	None	N
V/T	0.1143	likely_benign	0.0963	benign	-0.692	Destabilizing	0.155	N	0.237	neutral	None	None	None	None	N
V/W	0.7706	likely_pathogenic	0.7531	pathogenic	-0.818	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
V/Y	0.506	ambiguous	0.4954	ambiguous	-0.525	Destabilizing	0.999	D	0.69	prob.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.