TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24061	72406;72407;72408	chr2:178573951;178573950;178573949	chr2:179438678;179438677;179438676
N2AB	22420	67483;67484;67485	chr2:178573951;178573950;178573949	chr2:179438678;179438677;179438676
N2A	21493	64702;64703;64704	chr2:178573951;178573950;178573949	chr2:179438678;179438677;179438676
N2B	14996	45211;45212;45213	chr2:178573951;178573950;178573949	chr2:179438678;179438677;179438676
Novex-1	15121	45586;45587;45588	chr2:178573951;178573950;178573949	chr2:179438678;179438677;179438676
Novex-2	15188	45787;45788;45789	chr2:178573951;178573950;178573949	chr2:179438678;179438677;179438676
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-131
• Domain position: 33
• Structural Position: 46
• Q(SASA): 0.1759
• 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
M/I	None	None	0.001	N	0.271	0.153	0.228597637076	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
M/T	rs200471370	-1.528	0.425	N	0.567	0.397	None	gnomAD-2.1.1	1.35953E-04	None	None	None	None	N	None	1.65549E-04	0	None	0	0	None	0	None	0	2.58378E-04	1.40687E-04
M/T	rs200471370	-1.528	0.425	N	0.567	0.397	None	gnomAD-3.1.2	1.31631E-04	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	2.50103E-04	0	4.78469E-04
M/T	rs200471370	-1.528	0.425	N	0.567	0.397	None	gnomAD-4.0.0	2.91985E-04	None	None	None	None	N	None	6.68235E-05	1.66783E-05	None	0	0	None	0	0	3.39957E-04	0	1.02498E-03
M/V	rs201482015	-1.315	0.065	N	0.343	0.148	None	gnomAD-2.1.1	1.0732E-04	None	None	None	None	N	None	1.19973E-03	0	None	0	0	None	0	None	0	0	1.40687E-04
M/V	rs201482015	-1.315	0.065	N	0.343	0.148	None	gnomAD-3.1.2	3.87908E-04	None	None	None	None	N	None	1.39941E-03	6.55E-05	0	0	0	None	0	0	0	0	0
M/V	rs201482015	-1.315	0.065	N	0.343	0.148	None	1000 genomes	3.99361E-04	None	None	None	None	N	None	1.5E-03	0	None	None	0	0	None	None	None	0	None
M/V	rs201482015	-1.315	0.065	N	0.343	0.148	None	gnomAD-4.0.0	7.87176E-05	None	None	None	None	N	None	1.4796E-03	5.001E-05	None	0	0	None	0	0	3.39108E-06	0	1.44083E-04

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
M/A	0.5044	ambiguous	0.513	ambiguous	-2.198	Highly Destabilizing	0.3	N	0.473	neutral	None	None	None	None	N
M/C	0.7273	likely_pathogenic	0.7134	pathogenic	-2.185	Highly Destabilizing	0.981	D	0.683	prob.neutral	None	None	None	None	N
M/D	0.9821	likely_pathogenic	0.9789	pathogenic	-1.604	Destabilizing	0.936	D	0.733	prob.delet.	None	None	None	None	N
M/E	0.8554	likely_pathogenic	0.845	pathogenic	-1.462	Destabilizing	0.936	D	0.687	prob.neutral	None	None	None	None	N
M/F	0.4823	ambiguous	0.4802	ambiguous	-0.892	Destabilizing	0.495	N	0.525	neutral	None	None	None	None	N
M/G	0.8498	likely_pathogenic	0.8516	pathogenic	-2.628	Highly Destabilizing	0.936	D	0.701	prob.neutral	None	None	None	None	N
M/H	0.884	likely_pathogenic	0.8717	pathogenic	-2.009	Highly Destabilizing	0.981	D	0.737	prob.delet.	None	None	None	None	N
M/I	0.3624	ambiguous	0.3734	ambiguous	-1.005	Destabilizing	0.001	N	0.271	neutral	N	0.298226193	None	None	N
M/K	0.5302	ambiguous	0.5437	ambiguous	-1.154	Destabilizing	0.6	D	0.601	neutral	N	0.438205156	None	None	N
M/L	0.1518	likely_benign	0.1524	benign	-1.005	Destabilizing	0.001	N	0.229	neutral	N	0.38117565	None	None	N
M/N	0.9046	likely_pathogenic	0.8937	pathogenic	-1.274	Destabilizing	0.936	D	0.709	prob.delet.	None	None	None	None	N
M/P	0.9255	likely_pathogenic	0.9163	pathogenic	-1.38	Destabilizing	0.936	D	0.705	prob.neutral	None	None	None	None	N
M/Q	0.6422	likely_pathogenic	0.6187	pathogenic	-1.158	Destabilizing	0.936	D	0.561	neutral	None	None	None	None	N
M/R	0.5597	ambiguous	0.5662	pathogenic	-1.03	Destabilizing	0.784	D	0.617	neutral	N	0.511201405	None	None	N
M/S	0.7167	likely_pathogenic	0.7231	pathogenic	-1.917	Destabilizing	0.665	D	0.602	neutral	None	None	None	None	N
M/T	0.3129	likely_benign	0.3281	benign	-1.647	Destabilizing	0.425	N	0.567	neutral	N	0.423313061	None	None	N
M/V	0.0814	likely_benign	0.0836	benign	-1.38	Destabilizing	0.065	N	0.343	neutral	N	0.297409756	None	None	N
M/W	0.8181	likely_pathogenic	0.8227	pathogenic	-1.035	Destabilizing	0.995	D	0.685	prob.neutral	None	None	None	None	N
M/Y	0.8043	likely_pathogenic	0.7921	pathogenic	-1.027	Destabilizing	0.828	D	0.62	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.