TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15788	47587;47588;47589	chr2:178617989;178617988;178617987	chr2:179482716;179482715;179482714
N2AB	14147	42664;42665;42666	chr2:178617989;178617988;178617987	chr2:179482716;179482715;179482714
N2A	13220	39883;39884;39885	chr2:178617989;178617988;178617987	chr2:179482716;179482715;179482714
N2B	6723	20392;20393;20394	chr2:178617989;178617988;178617987	chr2:179482716;179482715;179482714
Novex-1	6848	20767;20768;20769	chr2:178617989;178617988;178617987	chr2:179482716;179482715;179482714
Novex-2	6915	20968;20969;20970	chr2:178617989;178617988;178617987	chr2:179482716;179482715;179482714
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-2
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.255
• Predicted PPI site: I

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/G	rs2057660238	None	0.09	N	0.611	0.183	0.203808441222	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
A/G	rs2057660238	None	0.09	N	0.611	0.183	0.203808441222	gnomAD-4.0.0	1.31721E-05	None	None	None	None	I	None	4.83209E-05	0	None	0	0	None	0	0	0	0	0
A/T	None	None	0.09	N	0.605	0.134	0.201204373187	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31251E-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	0.4501	ambiguous	0.3634	ambiguous	-0.937	Destabilizing	0.005	N	0.437	neutral	None	None	None	None	I
A/D	0.5519	ambiguous	0.5006	ambiguous	-1.365	Destabilizing	0.324	N	0.681	prob.neutral	N	0.46115933	None	None	I
A/E	0.4348	ambiguous	0.3628	ambiguous	-1.469	Destabilizing	0.388	N	0.64	neutral	None	None	None	None	I
A/F	0.4949	ambiguous	0.3442	ambiguous	-1.29	Destabilizing	0.818	D	0.687	prob.neutral	None	None	None	None	I
A/G	0.2196	likely_benign	0.2059	benign	-1.069	Destabilizing	0.09	N	0.611	neutral	N	0.443567509	None	None	I
A/H	0.6518	likely_pathogenic	0.5106	ambiguous	-1.125	Destabilizing	0.944	D	0.673	neutral	None	None	None	None	I
A/I	0.42	ambiguous	0.3346	benign	-0.638	Destabilizing	0.69	D	0.656	neutral	None	None	None	None	I
A/K	0.7468	likely_pathogenic	0.6685	pathogenic	-1.16	Destabilizing	0.241	N	0.64	neutral	None	None	None	None	I
A/L	0.2439	likely_benign	0.193	benign	-0.638	Destabilizing	0.241	N	0.605	neutral	None	None	None	None	I
A/M	0.2748	likely_benign	0.2026	benign	-0.404	Destabilizing	0.932	D	0.64	neutral	None	None	None	None	I
A/N	0.4213	ambiguous	0.3333	benign	-0.815	Destabilizing	0.241	N	0.686	prob.neutral	None	None	None	None	I
A/P	0.9289	likely_pathogenic	0.943	pathogenic	-0.69	Destabilizing	0.773	D	0.665	neutral	N	0.477905314	None	None	I
A/Q	0.4869	ambiguous	0.3982	ambiguous	-1.125	Destabilizing	0.69	D	0.667	neutral	None	None	None	None	I
A/R	0.6423	likely_pathogenic	0.574	pathogenic	-0.655	Destabilizing	0.69	D	0.663	neutral	None	None	None	None	I
A/S	0.0949	likely_benign	0.083	benign	-1.07	Destabilizing	0.001	N	0.259	neutral	N	0.306995559	None	None	I
A/T	0.0998	likely_benign	0.0872	benign	-1.102	Destabilizing	0.09	N	0.605	neutral	N	0.429648712	None	None	I
A/V	0.1916	likely_benign	0.1596	benign	-0.69	Destabilizing	0.193	N	0.645	neutral	N	0.478101923	None	None	I
A/W	0.8501	likely_pathogenic	0.761	pathogenic	-1.48	Destabilizing	0.981	D	0.707	prob.neutral	None	None	None	None	I
A/Y	0.6314	likely_pathogenic	0.4874	ambiguous	-1.141	Destabilizing	0.932	D	0.687	prob.neutral	None	None	None	None	I

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.