TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33327	100204;100205;100206	chr2:178537130;178537129;178537128	chr2:179401857;179401856;179401855
N2AB	31686	95281;95282;95283	chr2:178537130;178537129;178537128	chr2:179401857;179401856;179401855
N2A	30759	92500;92501;92502	chr2:178537130;178537129;178537128	chr2:179401857;179401856;179401855
N2B	24262	73009;73010;73011	chr2:178537130;178537129;178537128	chr2:179401857;179401856;179401855
Novex-1	24387	73384;73385;73386	chr2:178537130;178537129;178537128	chr2:179401857;179401856;179401855
Novex-2	24454	73585;73586;73587	chr2:178537130;178537129;178537128	chr2:179401857;179401856;179401855
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: Fn3-130
• Domain position: 38
• Structural Position: 39
• Q(SASA): 0.1497
• 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
V/L	rs1219652014	-0.911	0.099	N	0.434	0.113	0.400756358115	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
V/L	rs1219652014	-0.911	0.099	N	0.434	0.113	0.400756358115	gnomAD-4.0.0	1.59208E-06	None	None	None	None	N	None	0	2.28948E-05	None	0	0	None	0	0	0	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
V/A	0.7097	likely_pathogenic	0.613	pathogenic	-2.227	Highly Destabilizing	0.201	N	0.491	neutral	N	0.50866724	None	None	N
V/C	0.9229	likely_pathogenic	0.9133	pathogenic	-2.08	Highly Destabilizing	0.992	D	0.649	neutral	None	None	None	None	N
V/D	0.9539	likely_pathogenic	0.9246	pathogenic	-2.669	Highly Destabilizing	0.85	D	0.719	prob.delet.	None	None	None	None	N
V/E	0.854	likely_pathogenic	0.7807	pathogenic	-2.52	Highly Destabilizing	0.549	D	0.678	prob.neutral	N	0.483536722	None	None	N
V/F	0.5757	likely_pathogenic	0.4616	ambiguous	-1.492	Destabilizing	0.85	D	0.72	prob.delet.	None	None	None	None	N
V/G	0.8708	likely_pathogenic	0.836	pathogenic	-2.679	Highly Destabilizing	0.379	N	0.706	prob.neutral	N	0.488485535	None	None	N
V/H	0.9403	likely_pathogenic	0.9062	pathogenic	-2.16	Highly Destabilizing	0.977	D	0.682	prob.neutral	None	None	None	None	N
V/I	0.0788	likely_benign	0.0749	benign	-0.993	Destabilizing	0.001	N	0.187	neutral	None	None	None	None	N
V/K	0.8487	likely_pathogenic	0.7719	pathogenic	-1.854	Destabilizing	0.447	N	0.69	prob.neutral	None	None	None	None	N
V/L	0.4763	ambiguous	0.3661	ambiguous	-0.993	Destabilizing	0.099	N	0.434	neutral	N	0.459470571	None	None	N
V/M	0.3949	ambiguous	0.3063	benign	-1.126	Destabilizing	0.81	D	0.67	neutral	N	0.50970739	None	None	N
V/N	0.8711	likely_pathogenic	0.8165	pathogenic	-2.069	Highly Destabilizing	0.739	D	0.713	prob.delet.	None	None	None	None	N
V/P	0.9965	likely_pathogenic	0.9924	pathogenic	-1.377	Destabilizing	0.92	D	0.674	neutral	None	None	None	None	N
V/Q	0.8308	likely_pathogenic	0.7587	pathogenic	-2.057	Highly Destabilizing	0.85	D	0.655	neutral	None	None	None	None	N
V/R	0.7707	likely_pathogenic	0.6807	pathogenic	-1.476	Destabilizing	0.85	D	0.702	prob.neutral	None	None	None	None	N
V/S	0.7976	likely_pathogenic	0.7505	pathogenic	-2.706	Highly Destabilizing	0.021	N	0.551	neutral	None	None	None	None	N
V/T	0.5616	ambiguous	0.4885	ambiguous	-2.427	Highly Destabilizing	0.447	N	0.609	neutral	None	None	None	None	N
V/W	0.9746	likely_pathogenic	0.9581	pathogenic	-1.83	Destabilizing	0.992	D	0.692	prob.neutral	None	None	None	None	N
V/Y	0.9115	likely_pathogenic	0.8668	pathogenic	-1.529	Destabilizing	0.972	D	0.701	prob.neutral	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.