TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17253	51982;51983;51984	chr2:178609553;178609552;178609551	chr2:179474280;179474279;179474278
N2AB	15612	47059;47060;47061	chr2:178609553;178609552;178609551	chr2:179474280;179474279;179474278
N2A	14685	44278;44279;44280	chr2:178609553;178609552;178609551	chr2:179474280;179474279;179474278
N2B	8188	24787;24788;24789	chr2:178609553;178609552;178609551	chr2:179474280;179474279;179474278
Novex-1	8313	25162;25163;25164	chr2:178609553;178609552;178609551	chr2:179474280;179474279;179474278
Novex-2	8380	25363;25364;25365	chr2:178609553;178609552;178609551	chr2:179474280;179474279;179474278
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-112
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.7608
• 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
L/P	None	None	0.968	N	0.785	0.533	0.869023813792	gnomAD-4.0.0	3.20605E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.76027E-06	0	0
L/Q	rs747840389	-0.36	0.83	N	0.775	0.442	0.805105696268	gnomAD-2.1.1	4.1E-06	None	None	None	None	I	None	0	2.92E-05	None	0	0	None	0	None	0	0	0
L/Q	rs747840389	-0.36	0.83	N	0.775	0.442	0.805105696268	gnomAD-4.0.0	1.60303E-06	None	None	None	None	I	None	0	2.2997E-05	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
L/A	0.794	likely_pathogenic	0.838	pathogenic	-2.32	Highly Destabilizing	0.48	N	0.715	prob.delet.	None	None	None	None	I
L/C	0.8135	likely_pathogenic	0.8444	pathogenic	-1.553	Destabilizing	0.993	D	0.737	prob.delet.	None	None	None	None	I
L/D	0.9939	likely_pathogenic	0.9952	pathogenic	-2.124	Highly Destabilizing	0.929	D	0.783	deleterious	None	None	None	None	I
L/E	0.9701	likely_pathogenic	0.976	pathogenic	-1.986	Destabilizing	0.929	D	0.785	deleterious	None	None	None	None	I
L/F	0.5054	ambiguous	0.5428	ambiguous	-1.421	Destabilizing	0.866	D	0.749	deleterious	None	None	None	None	I
L/G	0.9292	likely_pathogenic	0.9455	pathogenic	-2.799	Highly Destabilizing	0.866	D	0.792	deleterious	None	None	None	None	I
L/H	0.9277	likely_pathogenic	0.943	pathogenic	-2.138	Highly Destabilizing	0.993	D	0.768	deleterious	None	None	None	None	I
L/I	0.2469	likely_benign	0.2694	benign	-0.988	Destabilizing	0.48	N	0.593	neutral	None	None	None	None	I
L/K	0.9324	likely_pathogenic	0.947	pathogenic	-1.734	Destabilizing	0.866	D	0.783	deleterious	None	None	None	None	I
L/M	0.1754	likely_benign	0.2013	benign	-0.837	Destabilizing	0.041	N	0.224	neutral	N	0.507046379	None	None	I
L/N	0.9597	likely_pathogenic	0.9699	pathogenic	-1.786	Destabilizing	0.929	D	0.788	deleterious	None	None	None	None	I
L/P	0.9124	likely_pathogenic	0.9273	pathogenic	-1.407	Destabilizing	0.968	D	0.785	deleterious	N	0.507154854	None	None	I
L/Q	0.8545	likely_pathogenic	0.8842	pathogenic	-1.782	Destabilizing	0.83	D	0.775	deleterious	N	0.506647875	None	None	I
L/R	0.9098	likely_pathogenic	0.9283	pathogenic	-1.317	Destabilizing	0.83	D	0.769	deleterious	N	0.506647875	None	None	I
L/S	0.9135	likely_pathogenic	0.9388	pathogenic	-2.503	Highly Destabilizing	0.866	D	0.778	deleterious	None	None	None	None	I
L/T	0.7619	likely_pathogenic	0.8238	pathogenic	-2.229	Highly Destabilizing	0.866	D	0.769	deleterious	None	None	None	None	I
L/V	0.2763	likely_benign	0.312	benign	-1.407	Destabilizing	0.41	N	0.613	neutral	N	0.492756674	None	None	I
L/W	0.8823	likely_pathogenic	0.9043	pathogenic	-1.684	Destabilizing	0.993	D	0.763	deleterious	None	None	None	None	I
L/Y	0.9203	likely_pathogenic	0.9303	pathogenic	-1.428	Destabilizing	0.929	D	0.785	deleterious	None	None	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.