TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21766	65521;65522;65523	chr2:178583886;178583885;178583884	chr2:179448613;179448612;179448611
N2AB	20125	60598;60599;60600	chr2:178583886;178583885;178583884	chr2:179448613;179448612;179448611
N2A	19198	57817;57818;57819	chr2:178583886;178583885;178583884	chr2:179448613;179448612;179448611
N2B	12701	38326;38327;38328	chr2:178583886;178583885;178583884	chr2:179448613;179448612;179448611
Novex-1	12826	38701;38702;38703	chr2:178583886;178583885;178583884	chr2:179448613;179448612;179448611
Novex-2	12893	38902;38903;38904	chr2:178583886;178583885;178583884	chr2:179448613;179448612;179448611
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: Fn3-46
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.1606
• 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/F	None	None	0.988	N	0.646	0.41	0.678861936705	gnomAD-4.0.0	1.66925E-06	None	None	None	None	N	None	0	0	None	4.96524E-05	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	0.356	ambiguous	0.3372	benign	-1.261	Destabilizing	0.134	N	0.239	neutral	N	0.460396077	None	None	N
V/C	0.856	likely_pathogenic	0.8216	pathogenic	-0.986	Destabilizing	0.999	D	0.639	neutral	None	None	None	None	N
V/D	0.8667	likely_pathogenic	0.8681	pathogenic	-0.807	Destabilizing	0.988	D	0.706	prob.neutral	N	0.497989551	None	None	N
V/E	0.8049	likely_pathogenic	0.7997	pathogenic	-0.78	Destabilizing	0.969	D	0.645	neutral	None	None	None	None	N
V/F	0.4738	ambiguous	0.3926	ambiguous	-0.824	Destabilizing	0.988	D	0.646	neutral	N	0.508150407	None	None	N
V/G	0.5334	ambiguous	0.5559	ambiguous	-1.602	Destabilizing	0.92	D	0.642	neutral	N	0.500596444	None	None	N
V/H	0.9369	likely_pathogenic	0.923	pathogenic	-1.036	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
V/I	0.0961	likely_benign	0.0817	benign	-0.427	Destabilizing	0.134	N	0.274	neutral	N	0.475866962	None	None	N
V/K	0.8384	likely_pathogenic	0.8291	pathogenic	-1.099	Destabilizing	0.969	D	0.639	neutral	None	None	None	None	N
V/L	0.4733	ambiguous	0.3944	ambiguous	-0.427	Destabilizing	0.704	D	0.431	neutral	N	0.506747229	None	None	N
V/M	0.3713	ambiguous	0.2997	benign	-0.446	Destabilizing	0.991	D	0.529	neutral	None	None	None	None	N
V/N	0.7623	likely_pathogenic	0.739	pathogenic	-0.97	Destabilizing	0.997	D	0.713	prob.delet.	None	None	None	None	N
V/P	0.4282	ambiguous	0.4199	ambiguous	-0.669	Destabilizing	0.02	N	0.455	neutral	None	None	None	None	N
V/Q	0.8403	likely_pathogenic	0.8213	pathogenic	-1.052	Destabilizing	0.997	D	0.685	prob.neutral	None	None	None	None	N
V/R	0.8144	likely_pathogenic	0.8122	pathogenic	-0.662	Destabilizing	0.991	D	0.715	prob.delet.	None	None	None	None	N
V/S	0.6729	likely_pathogenic	0.6457	pathogenic	-1.552	Destabilizing	0.884	D	0.591	neutral	None	None	None	None	N
V/T	0.5539	ambiguous	0.5071	ambiguous	-1.396	Destabilizing	0.939	D	0.529	neutral	None	None	None	None	N
V/W	0.9512	likely_pathogenic	0.9311	pathogenic	-1.018	Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
V/Y	0.828	likely_pathogenic	0.7937	pathogenic	-0.708	Destabilizing	0.997	D	0.656	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.