TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9414	28465;28466;28467	chr2:178710857;178710856;178710855	chr2:179575584;179575583;179575582
N2AB	9097	27514;27515;27516	chr2:178710857;178710856;178710855	chr2:179575584;179575583;179575582
N2A	8170	24733;24734;24735	chr2:178710857;178710856;178710855	chr2:179575584;179575583;179575582
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: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-80
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.3158
• 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
A/V	None	None	0.046	None	0.275	0.153	0.16115917748	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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
A/C	0.5507	ambiguous	0.5988	pathogenic	-1.129	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	N
A/D	0.8712	likely_pathogenic	0.8803	pathogenic	-0.9	Destabilizing	0.997	D	0.82	deleterious	None	None	None	None	N
A/E	0.7778	likely_pathogenic	0.8009	pathogenic	-0.893	Destabilizing	0.993	D	0.817	deleterious	None	None	None	None	N
A/F	0.6411	likely_pathogenic	0.6553	pathogenic	-0.972	Destabilizing	0.993	D	0.826	deleterious	None	None	None	None	N
A/G	0.1856	likely_benign	0.2179	benign	-1.23	Destabilizing	0.969	D	0.673	neutral	None	None	None	None	N
A/H	0.8723	likely_pathogenic	0.901	pathogenic	-1.356	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
A/I	0.3143	likely_benign	0.3061	benign	-0.231	Destabilizing	0.386	N	0.391	neutral	None	None	None	None	N
A/K	0.8411	likely_pathogenic	0.8759	pathogenic	-1.132	Destabilizing	0.993	D	0.82	deleterious	None	None	None	None	N
A/L	0.3079	likely_benign	0.3345	benign	-0.231	Destabilizing	0.807	D	0.58	neutral	None	None	None	None	N
A/M	0.3611	ambiguous	0.3789	ambiguous	-0.326	Destabilizing	0.993	D	0.797	deleterious	None	None	None	None	N
A/N	0.784	likely_pathogenic	0.8171	pathogenic	-0.933	Destabilizing	0.998	D	0.823	deleterious	None	None	None	None	N
A/P	0.8811	likely_pathogenic	0.8941	pathogenic	-0.418	Destabilizing	0.997	D	0.821	deleterious	None	None	None	None	N
A/Q	0.7551	likely_pathogenic	0.8046	pathogenic	-1.006	Destabilizing	0.998	D	0.804	deleterious	None	None	None	None	N
A/R	0.7475	likely_pathogenic	0.7997	pathogenic	-0.891	Destabilizing	0.998	D	0.819	deleterious	None	None	None	None	N
A/S	0.1875	likely_benign	0.2054	benign	-1.393	Destabilizing	0.969	D	0.675	neutral	None	None	None	None	N
A/T	0.1262	likely_benign	0.1278	benign	-1.261	Destabilizing	0.939	D	0.68	prob.neutral	None	None	None	None	N
A/V	0.133	likely_benign	0.1344	benign	-0.418	Destabilizing	0.046	N	0.275	neutral	None	None	None	None	N
A/W	0.9287	likely_pathogenic	0.9401	pathogenic	-1.316	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	N
A/Y	0.8416	likely_pathogenic	0.8587	pathogenic	-0.885	Destabilizing	0.998	D	0.821	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.