TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8671	26236;26237;26238	chr2:178715175;178715174;178715173	chr2:179579902;179579901;179579900
N2AB	8354	25285;25286;25287	chr2:178715175;178715174;178715173	chr2:179579902;179579901;179579900
N2A	7427	22504;22505;22506	chr2:178715175;178715174;178715173	chr2:179579902;179579901;179579900
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: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-72
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.7321
• 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
P/A	rs373927854	-0.207	0.998	D	0.662	0.436	0.349870743963	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	5.56E-05	None	0	None	0	0	0
P/L	rs2077292301	None	1.0	N	0.685	0.491	0.746293652351	gnomAD-4.0.0	1.59142E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85873E-06	0	0
P/S	None	None	1.0	N	0.679	0.473	0.362960570912	gnomAD-4.0.0	2.40065E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.62501E-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
P/A	0.2806	likely_benign	0.2221	benign	-0.661	Destabilizing	0.998	D	0.662	neutral	D	0.534654268	None	None	I
P/C	0.8987	likely_pathogenic	0.8654	pathogenic	-0.313	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	I
P/D	0.7919	likely_pathogenic	0.7265	pathogenic	-0.753	Destabilizing	0.998	D	0.657	neutral	None	None	None	None	I
P/E	0.7168	likely_pathogenic	0.6273	pathogenic	-0.836	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	I
P/F	0.8958	likely_pathogenic	0.8483	pathogenic	-0.801	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	I
P/G	0.7261	likely_pathogenic	0.6467	pathogenic	-0.833	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
P/H	0.6251	likely_pathogenic	0.5426	ambiguous	-0.498	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	I
P/I	0.7187	likely_pathogenic	0.6675	pathogenic	-0.33	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	I
P/K	0.7834	likely_pathogenic	0.6956	pathogenic	-0.579	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	I
P/L	0.421	ambiguous	0.3554	ambiguous	-0.33	Destabilizing	1.0	D	0.685	prob.neutral	N	0.494264385	None	None	I
P/M	0.7509	likely_pathogenic	0.7002	pathogenic	-0.347	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	I
P/N	0.7306	likely_pathogenic	0.6726	pathogenic	-0.165	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
P/Q	0.5757	likely_pathogenic	0.4884	ambiguous	-0.407	Destabilizing	1.0	D	0.647	neutral	N	0.482841946	None	None	I
P/R	0.6104	likely_pathogenic	0.5006	ambiguous	-0.083	Destabilizing	1.0	D	0.673	neutral	D	0.535886419	None	None	I
P/S	0.4377	ambiguous	0.3571	ambiguous	-0.447	Destabilizing	1.0	D	0.679	prob.neutral	N	0.489718481	None	None	I
P/T	0.3841	ambiguous	0.3273	benign	-0.441	Destabilizing	1.0	D	0.673	neutral	N	0.517703303	None	None	I
P/V	0.5584	ambiguous	0.4902	ambiguous	-0.407	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	I
P/W	0.9603	likely_pathogenic	0.9394	pathogenic	-0.931	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	I
P/Y	0.8587	likely_pathogenic	0.8022	pathogenic	-0.635	Destabilizing	1.0	D	0.64	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.