TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22463	67612;67613;67614	chr2:178579810;178579809;178579808	chr2:179444537;179444536;179444535
N2AB	20822	62689;62690;62691	chr2:178579810;178579809;178579808	chr2:179444537;179444536;179444535
N2A	19895	59908;59909;59910	chr2:178579810;178579809;178579808	chr2:179444537;179444536;179444535
N2B	13398	40417;40418;40419	chr2:178579810;178579809;178579808	chr2:179444537;179444536;179444535
Novex-1	13523	40792;40793;40794	chr2:178579810;178579809;178579808	chr2:179444537;179444536;179444535
Novex-2	13590	40993;40994;40995	chr2:178579810;178579809;178579808	chr2:179444537;179444536;179444535
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-51
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.3751
• 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	rs1162620445	-0.384	None	N	0.063	0.099	0.0762999501168	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14705E-04	0	None	0	0	None	0	None	0	0	0
V/L	rs1162620445	-0.384	None	N	0.063	0.099	0.0762999501168	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/L	rs1162620445	-0.384	None	N	0.063	0.099	0.0762999501168	gnomAD-4.0.0	6.57566E-06	None	None	None	None	N	None	2.41243E-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	0.2243	likely_benign	0.2043	benign	-0.913	Destabilizing	0.052	N	0.373	neutral	D	0.522196684	None	None	N
V/C	0.7262	likely_pathogenic	0.7011	pathogenic	-1.134	Destabilizing	0.935	D	0.319	neutral	None	None	None	None	N
V/D	0.6392	likely_pathogenic	0.6129	pathogenic	-1.165	Destabilizing	0.555	D	0.475	neutral	None	None	None	None	N
V/E	0.5048	ambiguous	0.5066	ambiguous	-1.233	Destabilizing	0.484	N	0.433	neutral	N	0.510392133	None	None	N
V/F	0.2364	likely_benign	0.2291	benign	-1.313	Destabilizing	0.235	N	0.387	neutral	None	None	None	None	N
V/G	0.2989	likely_benign	0.2815	benign	-1.08	Destabilizing	0.484	N	0.467	neutral	N	0.51191307	None	None	N
V/H	0.7266	likely_pathogenic	0.7038	pathogenic	-0.819	Destabilizing	0.935	D	0.414	neutral	None	None	None	None	N
V/I	0.0858	likely_benign	0.0784	benign	-0.585	Destabilizing	None	N	0.076	neutral	N	0.466705974	None	None	N
V/K	0.5141	ambiguous	0.4868	ambiguous	-0.631	Destabilizing	0.555	D	0.433	neutral	None	None	None	None	N
V/L	0.2333	likely_benign	0.2126	benign	-0.585	Destabilizing	None	N	0.063	neutral	N	0.468307819	None	None	N
V/M	0.206	likely_benign	0.1838	benign	-0.494	Destabilizing	0.38	N	0.398	neutral	None	None	None	None	N
V/N	0.4557	ambiguous	0.3898	ambiguous	-0.531	Destabilizing	0.555	D	0.465	neutral	None	None	None	None	N
V/P	0.7155	likely_pathogenic	0.6817	pathogenic	-0.663	Destabilizing	0.791	D	0.441	neutral	None	None	None	None	N
V/Q	0.4365	ambiguous	0.4395	ambiguous	-0.833	Destabilizing	0.791	D	0.413	neutral	None	None	None	None	N
V/R	0.4272	ambiguous	0.4131	ambiguous	-0.213	Destabilizing	0.555	D	0.459	neutral	None	None	None	None	N
V/S	0.2908	likely_benign	0.251	benign	-0.917	Destabilizing	0.081	N	0.433	neutral	None	None	None	None	N
V/T	0.2122	likely_benign	0.1846	benign	-0.891	Destabilizing	0.001	N	0.054	neutral	None	None	None	None	N
V/W	0.8891	likely_pathogenic	0.8897	pathogenic	-1.413	Destabilizing	0.935	D	0.52	neutral	None	None	None	None	N
V/Y	0.665	likely_pathogenic	0.649	pathogenic	-1.02	Destabilizing	0.555	D	0.365	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.