TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3198	9817;9818;9819	chr2:178766492;178766491;178766490	chr2:179631219;179631218;179631217
N2AB	3198	9817;9818;9819	chr2:178766492;178766491;178766490	chr2:179631219;179631218;179631217
N2A	3198	9817;9818;9819	chr2:178766492;178766491;178766490	chr2:179631219;179631218;179631217
N2B	3152	9679;9680;9681	chr2:178766492;178766491;178766490	chr2:179631219;179631218;179631217
Novex-1	3152	9679;9680;9681	chr2:178766492;178766491;178766490	chr2:179631219;179631218;179631217
Novex-2	3152	9679;9680;9681	chr2:178766492;178766491;178766490	chr2:179631219;179631218;179631217
Novex-3	3198	9817;9818;9819	chr2:178766492;178766491;178766490	chr2:179631219;179631218;179631217

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-22
• Domain position: 52
• Structural Position: 127
• Q(SASA): 0.3795
• 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	rs1035580252	None	0.884	D	0.553	0.318	0.572930072401	gnomAD-4.0.0	1.20035E-06	None	None	None	None	N	None	6.33473E-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	0.3884	ambiguous	0.4101	ambiguous	-1.271	Destabilizing	0.028	N	0.234	neutral	N	0.505038171	None	None	N
V/C	0.9381	likely_pathogenic	0.9478	pathogenic	-0.69	Destabilizing	0.996	D	0.51	neutral	None	None	None	None	N
V/D	0.8645	likely_pathogenic	0.8979	pathogenic	-1.197	Destabilizing	0.91	D	0.579	neutral	None	None	None	None	N
V/E	0.6684	likely_pathogenic	0.7313	pathogenic	-1.208	Destabilizing	0.884	D	0.565	neutral	N	0.509764227	None	None	N
V/F	0.5335	ambiguous	0.6205	pathogenic	-0.995	Destabilizing	0.91	D	0.535	neutral	None	None	None	None	N
V/G	0.668	likely_pathogenic	0.6847	pathogenic	-1.561	Destabilizing	0.684	D	0.571	neutral	N	0.508318961	None	None	N
V/H	0.9129	likely_pathogenic	0.9321	pathogenic	-1.118	Destabilizing	0.996	D	0.577	neutral	None	None	None	None	N
V/I	0.0975	likely_benign	0.1206	benign	-0.581	Destabilizing	0.004	N	0.233	neutral	None	None	None	None	N
V/K	0.6813	likely_pathogenic	0.7608	pathogenic	-1.13	Destabilizing	0.91	D	0.564	neutral	None	None	None	None	N
V/L	0.5513	ambiguous	0.6184	pathogenic	-0.581	Destabilizing	0.134	N	0.361	neutral	D	0.532895693	None	None	N
V/M	0.3292	likely_benign	0.3856	ambiguous	-0.403	Destabilizing	0.884	D	0.553	neutral	D	0.533917134	None	None	N
V/N	0.7307	likely_pathogenic	0.7915	pathogenic	-0.884	Destabilizing	0.91	D	0.597	neutral	None	None	None	None	N
V/P	0.9231	likely_pathogenic	0.929	pathogenic	-0.776	Destabilizing	0.953	D	0.587	neutral	None	None	None	None	N
V/Q	0.6513	likely_pathogenic	0.6944	pathogenic	-1.058	Destabilizing	0.953	D	0.589	neutral	None	None	None	None	N
V/R	0.6252	likely_pathogenic	0.7131	pathogenic	-0.582	Destabilizing	0.953	D	0.601	neutral	None	None	None	None	N
V/S	0.5235	ambiguous	0.5589	ambiguous	-1.322	Destabilizing	0.59	D	0.559	neutral	None	None	None	None	N
V/T	0.2832	likely_benign	0.2985	benign	-1.231	Destabilizing	0.016	N	0.238	neutral	None	None	None	None	N
V/W	0.9663	likely_pathogenic	0.9781	pathogenic	-1.206	Destabilizing	0.996	D	0.621	neutral	None	None	None	None	N
V/Y	0.9025	likely_pathogenic	0.9372	pathogenic	-0.913	Destabilizing	0.953	D	0.535	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.