TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32776	98551;98552;98553	chr2:178539739;178539738;178539737	chr2:179404466;179404465;179404464
N2AB	31135	93628;93629;93630	chr2:178539739;178539738;178539737	chr2:179404466;179404465;179404464
N2A	30208	90847;90848;90849	chr2:178539739;178539738;178539737	chr2:179404466;179404465;179404464
N2B	23711	71356;71357;71358	chr2:178539739;178539738;178539737	chr2:179404466;179404465;179404464
Novex-1	23836	71731;71732;71733	chr2:178539739;178539738;178539737	chr2:179404466;179404465;179404464
Novex-2	23903	71932;71933;71934	chr2:178539739;178539738;178539737	chr2:179404466;179404465;179404464
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-155
• Domain position: 69
• Structural Position: 157
• Q(SASA): 0.179
• 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/L	None	None	0.009	N	0.527	0.184	0.42538462244	gnomAD-4.0.0	1.08029E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.18125E-05	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	0.1483	likely_benign	0.1759	benign	-1.894	Destabilizing	None	N	0.311	neutral	N	0.50183256	None	None	N
V/C	0.5952	likely_pathogenic	0.6378	pathogenic	-1.192	Destabilizing	0.824	D	0.604	neutral	None	None	None	None	N
V/D	0.382	ambiguous	0.4483	ambiguous	-2.238	Highly Destabilizing	0.001	N	0.569	neutral	D	0.53180875	None	None	N
V/E	0.2507	likely_benign	0.2825	benign	-2.172	Highly Destabilizing	0.081	N	0.651	neutral	None	None	None	None	N
V/F	0.1335	likely_benign	0.1513	benign	-1.303	Destabilizing	0.317	N	0.665	neutral	N	0.52172783	None	None	N
V/G	0.2581	likely_benign	0.3058	benign	-2.286	Highly Destabilizing	0.062	N	0.675	prob.neutral	N	0.492506866	None	None	N
V/H	0.4171	ambiguous	0.4531	ambiguous	-1.979	Destabilizing	0.935	D	0.667	neutral	None	None	None	None	N
V/I	0.076	likely_benign	0.0771	benign	-0.866	Destabilizing	0.027	N	0.538	neutral	N	0.469856215	None	None	N
V/K	0.3744	ambiguous	0.4149	ambiguous	-1.701	Destabilizing	0.149	N	0.664	neutral	None	None	None	None	N
V/L	0.1249	likely_benign	0.1308	benign	-0.866	Destabilizing	0.009	N	0.527	neutral	N	0.454406759	None	None	N
V/M	0.1211	likely_benign	0.1253	benign	-0.608	Destabilizing	0.016	N	0.42	neutral	None	None	None	None	N
V/N	0.2583	likely_benign	0.2907	benign	-1.579	Destabilizing	0.235	N	0.69	prob.neutral	None	None	None	None	N
V/P	0.9163	likely_pathogenic	0.9436	pathogenic	-1.178	Destabilizing	0.38	N	0.663	neutral	None	None	None	None	N
V/Q	0.2448	likely_benign	0.2652	benign	-1.667	Destabilizing	0.555	D	0.676	prob.neutral	None	None	None	None	N
V/R	0.3209	likely_benign	0.3661	ambiguous	-1.226	Destabilizing	0.38	N	0.703	prob.neutral	None	None	None	None	N
V/S	0.167	likely_benign	0.1921	benign	-2.081	Highly Destabilizing	0.081	N	0.637	neutral	None	None	None	None	N
V/T	0.1479	likely_benign	0.1623	benign	-1.912	Destabilizing	0.002	N	0.431	neutral	None	None	None	None	N
V/W	0.7124	likely_pathogenic	0.7573	pathogenic	-1.674	Destabilizing	0.935	D	0.697	prob.neutral	None	None	None	None	N
V/Y	0.4175	ambiguous	0.4493	ambiguous	-1.384	Destabilizing	0.555	D	0.653	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.