TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1721	5386;5387;5388	chr2:178776703;178776702;178776701	chr2:179641430;179641429;179641428
N2AB	1721	5386;5387;5388	chr2:178776703;178776702;178776701	chr2:179641430;179641429;179641428
N2A	1721	5386;5387;5388	chr2:178776703;178776702;178776701	chr2:179641430;179641429;179641428
N2B	1675	5248;5249;5250	chr2:178776703;178776702;178776701	chr2:179641430;179641429;179641428
Novex-1	1675	5248;5249;5250	chr2:178776703;178776702;178776701	chr2:179641430;179641429;179641428
Novex-2	1675	5248;5249;5250	chr2:178776703;178776702;178776701	chr2:179641430;179641429;179641428
Novex-3	1721	5386;5387;5388	chr2:178776703;178776702;178776701	chr2:179641430;179641429;179641428

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-8
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.6841
• Predicted PPI site: I

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
H/R	rs1460034754	-0.372	1.0	N	0.676	0.584	0.368554958709	gnomAD-2.1.1	3.99E-06	None	None	None	None	I	None	0	0	None	0	5.45E-05	None	0	None	0	0	0
H/R	rs1460034754	-0.372	1.0	N	0.676	0.584	0.368554958709	gnomAD-4.0.0	2.7364E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69789E-06	1.15931E-05	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
H/A	0.7041	likely_pathogenic	0.691	pathogenic	-0.465	Destabilizing	0.999	D	0.63	neutral	None	None	None	None	I
H/C	0.4844	ambiguous	0.5186	ambiguous	0.155	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
H/D	0.7938	likely_pathogenic	0.7874	pathogenic	-0.267	Destabilizing	1.0	D	0.702	prob.neutral	D	0.587794784	None	None	I
H/E	0.759	likely_pathogenic	0.7346	pathogenic	-0.181	Destabilizing	0.999	D	0.575	neutral	None	None	None	None	I
H/F	0.6428	likely_pathogenic	0.6337	pathogenic	0.645	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
H/G	0.7728	likely_pathogenic	0.7798	pathogenic	-0.822	Destabilizing	0.999	D	0.649	neutral	None	None	None	None	I
H/I	0.7102	likely_pathogenic	0.7058	pathogenic	0.503	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
H/K	0.5858	likely_pathogenic	0.5594	ambiguous	-0.31	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	I
H/L	0.3803	ambiguous	0.3874	ambiguous	0.503	Stabilizing	1.0	D	0.685	prob.neutral	D	0.535318862	None	None	I
H/M	0.827	likely_pathogenic	0.8206	pathogenic	0.269	Stabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
H/N	0.3065	likely_benign	0.3118	benign	-0.441	Destabilizing	0.999	D	0.581	neutral	D	0.564477325	None	None	I
H/P	0.8683	likely_pathogenic	0.8845	pathogenic	0.203	Stabilizing	1.0	D	0.684	prob.neutral	D	0.712985528	None	None	I
H/Q	0.4506	ambiguous	0.4361	ambiguous	-0.234	Destabilizing	1.0	D	0.685	prob.neutral	D	0.538681203	None	None	I
H/R	0.2357	likely_benign	0.2184	benign	-0.831	Destabilizing	1.0	D	0.676	prob.neutral	N	0.498877913	None	None	I
H/S	0.5337	ambiguous	0.5218	ambiguous	-0.476	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	I
H/T	0.6069	likely_pathogenic	0.5956	pathogenic	-0.275	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
H/V	0.6164	likely_pathogenic	0.6177	pathogenic	0.203	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
H/W	0.748	likely_pathogenic	0.7452	pathogenic	0.904	Stabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	I
H/Y	0.2839	likely_benign	0.285	benign	1.016	Stabilizing	0.999	D	0.589	neutral	D	0.61140737	None	None	I

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.