TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17225	51898;51899;51900	chr2:178609750;178609749;178609748	chr2:179474477;179474476;179474475
N2AB	15584	46975;46976;46977	chr2:178609750;178609749;178609748	chr2:179474477;179474476;179474475
N2A	14657	44194;44195;44196	chr2:178609750;178609749;178609748	chr2:179474477;179474476;179474475
N2B	8160	24703;24704;24705	chr2:178609750;178609749;178609748	chr2:179474477;179474476;179474475
Novex-1	8285	25078;25079;25080	chr2:178609750;178609749;178609748	chr2:179474477;179474476;179474475
Novex-2	8352	25279;25280;25281	chr2:178609750;178609749;178609748	chr2:179474477;179474476;179474475
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-13
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.2151
• 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
E/D	None	None	0.999	N	0.483	0.363	0.357724736475	gnomAD-4.0.0	6.84727E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00071E-07	0	0
E/Q	rs2154198655	None	1.0	N	0.629	0.247	0.335414705075	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	3.16456E-03	0	0	0
E/Q	rs2154198655	None	1.0	N	0.629	0.247	0.335414705075	gnomAD-4.0.0	6.57704E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	3.40136E-03	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
E/A	0.6642	likely_pathogenic	0.5865	pathogenic	-1.003	Destabilizing	0.999	D	0.678	prob.neutral	N	0.467530443	None	None	I
E/C	0.9772	likely_pathogenic	0.9669	pathogenic	-0.71	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
E/D	0.9171	likely_pathogenic	0.9118	pathogenic	-1.617	Destabilizing	0.999	D	0.483	neutral	N	0.500993929	None	None	I
E/F	0.9772	likely_pathogenic	0.9649	pathogenic	-0.795	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	I
E/G	0.869	likely_pathogenic	0.8182	pathogenic	-1.397	Destabilizing	1.0	D	0.763	deleterious	N	0.491777217	None	None	I
E/H	0.9489	likely_pathogenic	0.925	pathogenic	-1.102	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	I
E/I	0.7692	likely_pathogenic	0.7081	pathogenic	0.088	Stabilizing	1.0	D	0.885	deleterious	None	None	None	None	I
E/K	0.6796	likely_pathogenic	0.5633	ambiguous	-1.085	Destabilizing	0.999	D	0.545	neutral	N	0.520423029	None	None	I
E/L	0.9004	likely_pathogenic	0.8672	pathogenic	0.088	Stabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
E/M	0.8399	likely_pathogenic	0.7974	pathogenic	0.685	Stabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
E/N	0.9505	likely_pathogenic	0.9429	pathogenic	-1.46	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	I
E/P	0.9989	likely_pathogenic	0.9985	pathogenic	-0.255	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
E/Q	0.3988	ambiguous	0.3298	benign	-1.266	Destabilizing	1.0	D	0.629	neutral	N	0.474531882	None	None	I
E/R	0.8071	likely_pathogenic	0.7003	pathogenic	-0.952	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
E/S	0.8297	likely_pathogenic	0.8013	pathogenic	-1.935	Destabilizing	0.999	D	0.586	neutral	None	None	None	None	I
E/T	0.8294	likely_pathogenic	0.7849	pathogenic	-1.587	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
E/V	0.5643	likely_pathogenic	0.4779	ambiguous	-0.255	Destabilizing	1.0	D	0.819	deleterious	N	0.434835911	None	None	I
E/W	0.9945	likely_pathogenic	0.9912	pathogenic	-0.78	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
E/Y	0.9718	likely_pathogenic	0.9588	pathogenic	-0.588	Destabilizing	1.0	D	0.846	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.