TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5715	17368;17369;17370	chr2:178731732;178731731;178731730	chr2:179596459;179596458;179596457
N2AB	5398	16417;16418;16419	chr2:178731732;178731731;178731730	chr2:179596459;179596458;179596457
N2A	4471	13636;13637;13638	chr2:178731732;178731731;178731730	chr2:179596459;179596458;179596457
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-40
• Domain position: 79
• Structural Position: 163
• Q(SASA): 0.7129
• 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
V/A	rs1279938466	None	0.999	N	0.586	0.373	0.46289702323	gnomAD-4.0.0	6.84394E-07	None	None	None	None	I	None	2.98793E-05	0	None	0	0	None	0	0	0	0	0
V/E	None	None	1.0	N	0.709	0.54	0.830966879155	gnomAD-4.0.0	4.10637E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.3983E-06	0	0
V/M	None	None	1.0	N	0.737	0.411	0.534814951121	gnomAD-4.0.0	2.05297E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79919E-06	0	1.65684E-05

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	0.219	likely_benign	0.2526	benign	-0.365	Destabilizing	0.999	D	0.586	neutral	N	0.503139282	None	None	I
V/C	0.9147	likely_pathogenic	0.9195	pathogenic	-0.842	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
V/D	0.8462	likely_pathogenic	0.8833	pathogenic	-0.404	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
V/E	0.7249	likely_pathogenic	0.7806	pathogenic	-0.524	Destabilizing	1.0	D	0.709	prob.delet.	N	0.489735389	None	None	I
V/F	0.3325	likely_benign	0.3891	ambiguous	-0.766	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	I
V/G	0.4111	ambiguous	0.4922	ambiguous	-0.409	Destabilizing	1.0	D	0.711	prob.delet.	N	0.495798549	None	None	I
V/H	0.899	likely_pathogenic	0.9169	pathogenic	-0.015	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
V/I	0.1359	likely_benign	0.1421	benign	-0.388	Destabilizing	0.998	D	0.519	neutral	None	None	None	None	I
V/K	0.8742	likely_pathogenic	0.8983	pathogenic	-0.409	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
V/L	0.6137	likely_pathogenic	0.6231	pathogenic	-0.388	Destabilizing	0.997	D	0.605	neutral	N	0.502659279	None	None	I
V/M	0.3805	ambiguous	0.4475	ambiguous	-0.606	Destabilizing	1.0	D	0.737	prob.delet.	N	0.489735389	None	None	I
V/N	0.7254	likely_pathogenic	0.7617	pathogenic	-0.217	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	I
V/P	0.9655	likely_pathogenic	0.9686	pathogenic	-0.354	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
V/Q	0.8165	likely_pathogenic	0.8472	pathogenic	-0.438	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
V/R	0.8124	likely_pathogenic	0.8328	pathogenic	0.047	Stabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
V/S	0.4759	ambiguous	0.531	ambiguous	-0.519	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
V/T	0.3347	likely_benign	0.3675	ambiguous	-0.552	Destabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	I
V/W	0.9394	likely_pathogenic	0.9568	pathogenic	-0.808	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
V/Y	0.7973	likely_pathogenic	0.828	pathogenic	-0.545	Destabilizing	1.0	D	0.708	prob.delet.	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.