TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15459	46600;46601;46602	chr2:178620042;178620041;178620040	chr2:179484769;179484768;179484767
N2AB	13818	41677;41678;41679	chr2:178620042;178620041;178620040	chr2:179484769;179484768;179484767
N2A	12891	38896;38897;38898	chr2:178620042;178620041;178620040	chr2:179484769;179484768;179484767
N2B	6394	19405;19406;19407	chr2:178620042;178620041;178620040	chr2:179484769;179484768;179484767
Novex-1	6519	19780;19781;19782	chr2:178620042;178620041;178620040	chr2:179484769;179484768;179484767
Novex-2	6586	19981;19982;19983	chr2:178620042;178620041;178620040	chr2:179484769;179484768;179484767
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-106
• Domain position: 69
• Structural Position: 153
• Q(SASA): 0.2588
• 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
E/Q	rs752596345	-0.824	1.0	N	0.617	0.388	0.345405024496	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.98E-06	0
E/Q	rs752596345	-0.824	1.0	N	0.617	0.388	0.345405024496	gnomAD-4.0.0	1.59515E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86518E-06	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	0.6783	likely_pathogenic	0.6742	pathogenic	-0.877	Destabilizing	0.999	D	0.685	prob.neutral	N	0.510874668	None	None	N
E/C	0.9887	likely_pathogenic	0.9897	pathogenic	-0.505	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/D	0.4823	ambiguous	0.513	ambiguous	-1.206	Destabilizing	0.999	D	0.564	neutral	N	0.511147514	None	None	N
E/F	0.9649	likely_pathogenic	0.9676	pathogenic	-0.519	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/G	0.8281	likely_pathogenic	0.817	pathogenic	-1.237	Destabilizing	1.0	D	0.738	prob.delet.	D	0.682813392	None	None	N
E/H	0.9435	likely_pathogenic	0.9469	pathogenic	-0.916	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
E/I	0.7313	likely_pathogenic	0.7623	pathogenic	0.104	Stabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
E/K	0.8196	likely_pathogenic	0.8037	pathogenic	-0.813	Destabilizing	0.999	D	0.625	neutral	N	0.505009886	None	None	N
E/L	0.8491	likely_pathogenic	0.8615	pathogenic	0.104	Stabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
E/M	0.8644	likely_pathogenic	0.8825	pathogenic	0.593	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/N	0.8447	likely_pathogenic	0.8436	pathogenic	-1.149	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
E/P	0.9464	likely_pathogenic	0.932	pathogenic	-0.201	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/Q	0.5743	likely_pathogenic	0.5719	pathogenic	-1.02	Destabilizing	1.0	D	0.617	neutral	N	0.511664359	None	None	N
E/R	0.8762	likely_pathogenic	0.8636	pathogenic	-0.619	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
E/S	0.7216	likely_pathogenic	0.7271	pathogenic	-1.495	Destabilizing	0.999	D	0.61	neutral	None	None	None	None	N
E/T	0.6842	likely_pathogenic	0.7097	pathogenic	-1.201	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/V	0.586	likely_pathogenic	0.6261	pathogenic	-0.201	Destabilizing	1.0	D	0.781	deleterious	N	0.511986766	None	None	N
E/W	0.9913	likely_pathogenic	0.991	pathogenic	-0.362	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/Y	0.9525	likely_pathogenic	0.9572	pathogenic	-0.299	Destabilizing	1.0	D	0.793	deleterious	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.