TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33313	100162;100163;100164	chr2:178537172;178537171;178537170	chr2:179401899;179401898;179401897
N2AB	31672	95239;95240;95241	chr2:178537172;178537171;178537170	chr2:179401899;179401898;179401897
N2A	30745	92458;92459;92460	chr2:178537172;178537171;178537170	chr2:179401899;179401898;179401897
N2B	24248	72967;72968;72969	chr2:178537172;178537171;178537170	chr2:179401899;179401898;179401897
Novex-1	24373	73342;73343;73344	chr2:178537172;178537171;178537170	chr2:179401899;179401898;179401897
Novex-2	24440	73543;73544;73545	chr2:178537172;178537171;178537170	chr2:179401899;179401898;179401897
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-130
• Domain position: 24
• Structural Position: 25
• Q(SASA): 0.4245
• 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
K/N	rs1691982544	None	0.83	N	0.694	0.162	0.151104730317	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	1.31113E-04	0	0	0	None	0	0	0	0	0
K/N	rs1691982544	None	0.83	N	0.694	0.162	0.151104730317	gnomAD-4.0.0	1.31454E-05	None	None	None	None	N	None	0	1.31113E-04	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
K/A	0.5292	ambiguous	0.5758	pathogenic	-0.292	Destabilizing	0.48	N	0.613	neutral	None	None	None	None	N
K/C	0.8288	likely_pathogenic	0.8651	pathogenic	-0.303	Destabilizing	0.993	D	0.765	deleterious	None	None	None	None	N
K/D	0.7265	likely_pathogenic	0.7314	pathogenic	0.012	Stabilizing	0.866	D	0.762	deleterious	None	None	None	None	N
K/E	0.2806	likely_benign	0.2708	benign	0.078	Stabilizing	0.41	N	0.515	neutral	N	0.503741423	None	None	N
K/F	0.8623	likely_pathogenic	0.8804	pathogenic	-0.139	Destabilizing	0.993	D	0.726	prob.delet.	None	None	None	None	N
K/G	0.6596	likely_pathogenic	0.7458	pathogenic	-0.609	Destabilizing	0.866	D	0.7	prob.neutral	None	None	None	None	N
K/H	0.4291	ambiguous	0.4385	ambiguous	-0.991	Destabilizing	0.961	D	0.745	deleterious	None	None	None	None	N
K/I	0.4982	ambiguous	0.4832	ambiguous	0.499	Stabilizing	0.908	D	0.759	deleterious	N	0.473080759	None	None	N
K/L	0.4272	ambiguous	0.4623	ambiguous	0.499	Stabilizing	0.866	D	0.7	prob.neutral	None	None	None	None	N
K/M	0.3057	likely_benign	0.3216	benign	0.347	Stabilizing	0.98	D	0.742	deleterious	None	None	None	None	N
K/N	0.4477	ambiguous	0.4705	ambiguous	-0.133	Destabilizing	0.83	D	0.694	prob.neutral	N	0.476557608	None	None	N
K/P	0.9571	likely_pathogenic	0.9518	pathogenic	0.266	Stabilizing	0.929	D	0.786	deleterious	None	None	None	None	N
K/Q	0.1522	likely_benign	0.1573	benign	-0.255	Destabilizing	0.01	N	0.288	neutral	N	0.491833705	None	None	N
K/R	0.1369	likely_benign	0.141	benign	-0.429	Destabilizing	0.41	N	0.54	neutral	N	0.508149952	None	None	N
K/S	0.5618	ambiguous	0.6005	pathogenic	-0.712	Destabilizing	0.48	N	0.589	neutral	None	None	None	None	N
K/T	0.3171	likely_benign	0.3103	benign	-0.462	Destabilizing	0.83	D	0.767	deleterious	N	0.492775068	None	None	N
K/V	0.4892	ambiguous	0.4877	ambiguous	0.266	Stabilizing	0.866	D	0.735	prob.delet.	None	None	None	None	N
K/W	0.9297	likely_pathogenic	0.9348	pathogenic	-0.057	Destabilizing	0.993	D	0.765	deleterious	None	None	None	None	N
K/Y	0.7403	likely_pathogenic	0.7703	pathogenic	0.24	Stabilizing	0.929	D	0.765	deleterious	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.