TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9386	28381;28382;28383	chr2:178711080;178711079;178711078	chr2:179575807;179575806;179575805
N2AB	9069	27430;27431;27432	chr2:178711080;178711079;178711078	chr2:179575807;179575806;179575805
N2A	8142	24649;24650;24651	chr2:178711080;178711079;178711078	chr2:179575807;179575806;179575805
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: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-79
• Domain position: 86
• Structural Position: 172
• Q(SASA): 0.115
• 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/S	None	None	0.928	None	0.495	0.444	0.46512379133	gnomAD-4.0.0	1.64315E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.51254E-05	0
A/V	rs2076585967	None	0.989	None	0.667	0.387	0.519241965532	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

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	0.7657	likely_pathogenic	0.7537	pathogenic	-1.245	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
A/D	0.9769	likely_pathogenic	0.9809	pathogenic	-1.115	Destabilizing	0.978	D	0.859	deleterious	None	None	None	None	N
A/E	0.9753	likely_pathogenic	0.979	pathogenic	-1.054	Destabilizing	0.992	D	0.799	deleterious	None	None	None	None	N
A/F	0.9427	likely_pathogenic	0.9378	pathogenic	-0.895	Destabilizing	0.997	D	0.885	deleterious	None	None	None	None	N
A/G	0.1457	likely_benign	0.1566	benign	-1.318	Destabilizing	0.017	N	0.303	neutral	None	None	None	None	N
A/H	0.9857	likely_pathogenic	0.9846	pathogenic	-1.464	Destabilizing	0.999	D	0.871	deleterious	None	None	None	None	N
A/I	0.8868	likely_pathogenic	0.878	pathogenic	-0.084	Destabilizing	0.992	D	0.843	deleterious	None	None	None	None	N
A/K	0.9887	likely_pathogenic	0.9905	pathogenic	-1.035	Destabilizing	0.983	D	0.798	deleterious	None	None	None	None	N
A/L	0.8182	likely_pathogenic	0.8139	pathogenic	-0.084	Destabilizing	0.992	D	0.775	deleterious	None	None	None	None	N
A/M	0.8572	likely_pathogenic	0.8598	pathogenic	-0.29	Destabilizing	0.999	D	0.828	deleterious	None	None	None	None	N
A/N	0.951	likely_pathogenic	0.9543	pathogenic	-0.977	Destabilizing	0.983	D	0.863	deleterious	None	None	None	None	N
A/P	0.9883	likely_pathogenic	0.9885	pathogenic	-0.33	Destabilizing	0.996	D	0.84	deleterious	None	None	None	None	N
A/Q	0.9565	likely_pathogenic	0.9621	pathogenic	-0.992	Destabilizing	0.997	D	0.857	deleterious	None	None	None	None	N
A/R	0.9668	likely_pathogenic	0.9714	pathogenic	-0.906	Destabilizing	0.992	D	0.846	deleterious	None	None	None	None	N
A/S	0.2074	likely_benign	0.2042	benign	-1.499	Destabilizing	0.928	D	0.495	neutral	None	None	None	None	N
A/T	0.3822	ambiguous	0.4063	ambiguous	-1.308	Destabilizing	0.989	D	0.695	prob.neutral	None	None	None	None	N
A/V	0.5943	likely_pathogenic	0.5805	pathogenic	-0.33	Destabilizing	0.989	D	0.667	neutral	None	None	None	None	N
A/W	0.9959	likely_pathogenic	0.9954	pathogenic	-1.319	Destabilizing	0.999	D	0.881	deleterious	None	None	None	None	N
A/Y	0.9832	likely_pathogenic	0.9809	pathogenic	-0.84	Destabilizing	0.999	D	0.878	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.