TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21157	63694;63695;63696	chr2:178587938;178587937;178587936	chr2:179452665;179452664;179452663
N2AB	19516	58771;58772;58773	chr2:178587938;178587937;178587936	chr2:179452665;179452664;179452663
N2A	18589	55990;55991;55992	chr2:178587938;178587937;178587936	chr2:179452665;179452664;179452663
N2B	12092	36499;36500;36501	chr2:178587938;178587937;178587936	chr2:179452665;179452664;179452663
Novex-1	12217	36874;36875;36876	chr2:178587938;178587937;178587936	chr2:179452665;179452664;179452663
Novex-2	12284	37075;37076;37077	chr2:178587938;178587937;178587936	chr2:179452665;179452664;179452663
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-41
• Domain position: 94
• Structural Position: 121
• Q(SASA): 0.1153
• 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
A/T	rs1195739289	None	1.0	N	0.777	0.279	0.126345400529	gnomAD-4.0.0	1.60837E-06	None	None	None	None	N	None	5.69476E-05	0	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
A/C	0.4	ambiguous	0.4035	ambiguous	-0.906	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
A/D	0.6971	likely_pathogenic	0.6702	pathogenic	-2.069	Highly Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
A/E	0.552	ambiguous	0.5176	ambiguous	-1.956	Destabilizing	1.0	D	0.744	deleterious	N	0.506077147	None	None	N
A/F	0.559	ambiguous	0.5483	ambiguous	-0.825	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
A/G	0.1945	likely_benign	0.19	benign	-1.495	Destabilizing	1.0	D	0.634	neutral	N	0.478255827	None	None	N
A/H	0.7054	likely_pathogenic	0.6932	pathogenic	-1.897	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
A/I	0.3465	ambiguous	0.3391	benign	-0.084	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
A/K	0.7516	likely_pathogenic	0.7304	pathogenic	-1.362	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
A/L	0.2841	likely_benign	0.2882	benign	-0.084	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
A/M	0.2842	likely_benign	0.2884	benign	-0.109	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
A/N	0.53	ambiguous	0.5291	ambiguous	-1.36	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
A/P	0.9076	likely_pathogenic	0.9022	pathogenic	-0.38	Destabilizing	1.0	D	0.77	deleterious	N	0.46740036	None	None	N
A/Q	0.5186	ambiguous	0.5095	ambiguous	-1.316	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
A/R	0.6607	likely_pathogenic	0.62	pathogenic	-1.243	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
A/S	0.1238	likely_benign	0.1204	benign	-1.727	Destabilizing	1.0	D	0.631	neutral	N	0.363879024	None	None	N
A/T	0.1059	likely_benign	0.1033	benign	-1.514	Destabilizing	1.0	D	0.777	deleterious	N	0.486008519	None	None	N
A/V	0.1578	likely_benign	0.1518	benign	-0.38	Destabilizing	1.0	D	0.687	prob.neutral	N	0.480429341	None	None	N
A/W	0.8746	likely_pathogenic	0.8654	pathogenic	-1.506	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
A/Y	0.6973	likely_pathogenic	0.6907	pathogenic	-0.988	Destabilizing	1.0	D	0.825	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.