TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25224	75895;75896;75897	chr2:178570462;178570461;178570460	chr2:179435189;179435188;179435187
N2AB	23583	70972;70973;70974	chr2:178570462;178570461;178570460	chr2:179435189;179435188;179435187
N2A	22656	68191;68192;68193	chr2:178570462;178570461;178570460	chr2:179435189;179435188;179435187
N2B	16159	48700;48701;48702	chr2:178570462;178570461;178570460	chr2:179435189;179435188;179435187
Novex-1	16284	49075;49076;49077	chr2:178570462;178570461;178570460	chr2:179435189;179435188;179435187
Novex-2	16351	49276;49277;49278	chr2:178570462;178570461;178570460	chr2:179435189;179435188;179435187
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-71
• Domain position: 21
• Structural Position: 22
• Q(SASA): 0.0887
• 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
L/I	None	None	0.02	N	0.241	0.057	0.183819452728	gnomAD-4.0.0	6.00161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56251E-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
L/A	0.7694	likely_pathogenic	0.8324	pathogenic	-2.453	Highly Destabilizing	0.953	D	0.729	prob.delet.	None	None	None	None	N
L/C	0.7709	likely_pathogenic	0.8452	pathogenic	-1.912	Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
L/D	0.9994	likely_pathogenic	0.9996	pathogenic	-2.763	Highly Destabilizing	0.998	D	0.92	deleterious	None	None	None	None	N
L/E	0.9948	likely_pathogenic	0.9969	pathogenic	-2.462	Highly Destabilizing	0.998	D	0.914	deleterious	None	None	None	None	N
L/F	0.4458	ambiguous	0.5626	ambiguous	-1.473	Destabilizing	0.986	D	0.662	neutral	None	None	None	None	N
L/G	0.9803	likely_pathogenic	0.9881	pathogenic	-3.077	Highly Destabilizing	0.998	D	0.909	deleterious	None	None	None	None	N
L/H	0.9863	likely_pathogenic	0.9913	pathogenic	-2.742	Highly Destabilizing	0.999	D	0.909	deleterious	None	None	None	None	N
L/I	0.0788	likely_benign	0.0819	benign	-0.612	Destabilizing	0.02	N	0.241	neutral	N	0.514774854	None	None	N
L/K	0.9913	likely_pathogenic	0.9949	pathogenic	-1.797	Destabilizing	0.993	D	0.875	deleterious	None	None	None	None	N
L/M	0.2405	likely_benign	0.2774	benign	-0.774	Destabilizing	0.986	D	0.624	neutral	None	None	None	None	N
L/N	0.9959	likely_pathogenic	0.9973	pathogenic	-2.346	Highly Destabilizing	0.998	D	0.927	deleterious	None	None	None	None	N
L/P	0.9872	likely_pathogenic	0.993	pathogenic	-1.21	Destabilizing	0.997	D	0.93	deleterious	D	0.56264248	None	None	N
L/Q	0.9799	likely_pathogenic	0.9884	pathogenic	-2.039	Highly Destabilizing	0.997	D	0.911	deleterious	D	0.56264248	None	None	N
L/R	0.9791	likely_pathogenic	0.9879	pathogenic	-1.831	Destabilizing	0.997	D	0.891	deleterious	D	0.56264248	None	None	N
L/S	0.9797	likely_pathogenic	0.9863	pathogenic	-3.074	Highly Destabilizing	0.993	D	0.85	deleterious	None	None	None	None	N
L/T	0.8783	likely_pathogenic	0.9158	pathogenic	-2.593	Highly Destabilizing	0.986	D	0.769	deleterious	None	None	None	None	N
L/V	0.0718	likely_benign	0.082	benign	-1.21	Destabilizing	0.76	D	0.391	neutral	N	0.508230097	None	None	N
L/W	0.9446	likely_pathogenic	0.9672	pathogenic	-1.875	Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
L/Y	0.9476	likely_pathogenic	0.9704	pathogenic	-1.564	Destabilizing	0.998	D	0.749	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.