TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7385	22378;22379;22380	chr2:178722746;178722745;178722744	chr2:179587473;179587472;179587471
N2AB	7068	21427;21428;21429	chr2:178722746;178722745;178722744	chr2:179587473;179587472;179587471
N2A	6141	18646;18647;18648	chr2:178722746;178722745;178722744	chr2:179587473;179587472;179587471
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-58
• Domain position: 63
• Structural Position: 144
• Q(SASA): 0.1124
• 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
V/L	rs1273152724	-0.783	0.944	N	0.493	0.317	0.540153309661	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
V/L	rs1273152724	-0.783	0.944	N	0.493	0.317	0.540153309661	gnomAD-4.0.0	1.59266E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4339E-05	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
V/A	0.2307	likely_benign	0.3695	ambiguous	-2.173	Highly Destabilizing	0.734	D	0.296	neutral	N	0.450174376	None	None	N
V/C	0.8925	likely_pathogenic	0.9282	pathogenic	-2.158	Highly Destabilizing	1.0	D	0.574	neutral	None	None	None	None	N
V/D	0.9163	likely_pathogenic	0.9706	pathogenic	-2.773	Highly Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
V/E	0.8835	likely_pathogenic	0.9502	pathogenic	-2.534	Highly Destabilizing	1.0	D	0.609	neutral	D	0.530572843	None	None	N
V/F	0.6485	likely_pathogenic	0.8248	pathogenic	-1.383	Destabilizing	0.904	D	0.403	neutral	None	None	None	None	N
V/G	0.3838	ambiguous	0.5738	pathogenic	-2.728	Highly Destabilizing	0.999	D	0.639	neutral	D	0.523824894	None	None	N
V/H	0.9711	likely_pathogenic	0.9901	pathogenic	-2.503	Highly Destabilizing	1.0	D	0.656	neutral	None	None	None	None	N
V/I	0.1138	likely_benign	0.1362	benign	-0.606	Destabilizing	0.739	D	0.507	neutral	None	None	None	None	N
V/K	0.9316	likely_pathogenic	0.9737	pathogenic	-1.707	Destabilizing	1.0	D	0.609	neutral	None	None	None	None	N
V/L	0.4196	ambiguous	0.5623	ambiguous	-0.606	Destabilizing	0.944	D	0.493	neutral	N	0.48255894	None	None	N
V/M	0.344	ambiguous	0.485	ambiguous	-0.93	Destabilizing	1.0	D	0.565	neutral	N	0.507188669	None	None	N
V/N	0.792	likely_pathogenic	0.8889	pathogenic	-2.14	Highly Destabilizing	1.0	D	0.674	neutral	None	None	None	None	N
V/P	0.7808	likely_pathogenic	0.8791	pathogenic	-1.103	Destabilizing	1.0	D	0.607	neutral	None	None	None	None	N
V/Q	0.897	likely_pathogenic	0.9566	pathogenic	-1.941	Destabilizing	1.0	D	0.612	neutral	None	None	None	None	N
V/R	0.9141	likely_pathogenic	0.9649	pathogenic	-1.64	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	N
V/S	0.5099	ambiguous	0.6766	pathogenic	-2.807	Highly Destabilizing	0.993	D	0.599	neutral	None	None	None	None	N
V/T	0.3713	ambiguous	0.5056	ambiguous	-2.409	Highly Destabilizing	0.991	D	0.557	neutral	None	None	None	None	N
V/W	0.9858	likely_pathogenic	0.9953	pathogenic	-1.854	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	N
V/Y	0.9443	likely_pathogenic	0.9796	pathogenic	-1.498	Destabilizing	0.999	D	0.606	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.