TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20421	61486;61487;61488	chr2:178590464;178590463;178590462	chr2:179455191;179455190;179455189
N2AB	18780	56563;56564;56565	chr2:178590464;178590463;178590462	chr2:179455191;179455190;179455189
N2A	17853	53782;53783;53784	chr2:178590464;178590463;178590462	chr2:179455191;179455190;179455189
N2B	11356	34291;34292;34293	chr2:178590464;178590463;178590462	chr2:179455191;179455190;179455189
Novex-1	11481	34666;34667;34668	chr2:178590464;178590463;178590462	chr2:179455191;179455190;179455189
Novex-2	11548	34867;34868;34869	chr2:178590464;178590463;178590462	chr2:179455191;179455190;179455189
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-36
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.1741
• 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
I/T	None	None	0.961	N	0.502	0.347	0.467501455318	gnomAD-4.0.0	1.59277E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8609E-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
I/A	0.6996	likely_pathogenic	0.7187	pathogenic	-2.076	Highly Destabilizing	0.931	D	0.523	neutral	None	None	None	None	I
I/C	0.718	likely_pathogenic	0.7397	pathogenic	-1.203	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
I/D	0.9401	likely_pathogenic	0.9457	pathogenic	-1.967	Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	I
I/E	0.8511	likely_pathogenic	0.8639	pathogenic	-1.836	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	I
I/F	0.3799	ambiguous	0.3939	ambiguous	-1.342	Destabilizing	0.994	D	0.535	neutral	N	0.494110714	None	None	I
I/G	0.9207	likely_pathogenic	0.9313	pathogenic	-2.517	Highly Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	I
I/H	0.8334	likely_pathogenic	0.8599	pathogenic	-1.751	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
I/K	0.7599	likely_pathogenic	0.7817	pathogenic	-1.556	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	I
I/L	0.2032	likely_benign	0.2133	benign	-0.863	Destabilizing	0.689	D	0.383	neutral	N	0.442468385	None	None	I
I/M	0.1813	likely_benign	0.1918	benign	-0.629	Destabilizing	0.994	D	0.563	neutral	N	0.494457431	None	None	I
I/N	0.68	likely_pathogenic	0.6993	pathogenic	-1.665	Destabilizing	0.998	D	0.767	deleterious	N	0.474935231	None	None	I
I/P	0.9405	likely_pathogenic	0.9457	pathogenic	-1.242	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	I
I/Q	0.7704	likely_pathogenic	0.7977	pathogenic	-1.673	Destabilizing	0.999	D	0.76	deleterious	None	None	None	None	I
I/R	0.7213	likely_pathogenic	0.7523	pathogenic	-1.091	Destabilizing	0.999	D	0.768	deleterious	None	None	None	None	I
I/S	0.7188	likely_pathogenic	0.7434	pathogenic	-2.3	Highly Destabilizing	0.994	D	0.669	neutral	N	0.501018044	None	None	I
I/T	0.6268	likely_pathogenic	0.6595	pathogenic	-2.032	Highly Destabilizing	0.961	D	0.502	neutral	N	0.480546771	None	None	I
I/V	0.1049	likely_benign	0.1099	benign	-1.242	Destabilizing	0.122	N	0.204	neutral	N	0.364794249	None	None	I
I/W	0.8856	likely_pathogenic	0.9012	pathogenic	-1.592	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	I
I/Y	0.7552	likely_pathogenic	0.7634	pathogenic	-1.302	Destabilizing	0.999	D	0.675	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.