TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2311	7156;7157;7158	chr2:178774333;178774332;178774331	chr2:179639060;179639059;179639058
N2AB	2311	7156;7157;7158	chr2:178774333;178774332;178774331	chr2:179639060;179639059;179639058
N2A	2311	7156;7157;7158	chr2:178774333;178774332;178774331	chr2:179639060;179639059;179639058
N2B	2265	7018;7019;7020	chr2:178774333;178774332;178774331	chr2:179639060;179639059;179639058
Novex-1	2265	7018;7019;7020	chr2:178774333;178774332;178774331	chr2:179639060;179639059;179639058
Novex-2	2265	7018;7019;7020	chr2:178774333;178774332;178774331	chr2:179639060;179639059;179639058
Novex-3	2311	7156;7157;7158	chr2:178774333;178774332;178774331	chr2:179639060;179639059;179639058

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-12
• Domain position: 45
• Structural Position: 115
• Q(SASA): 0.2842
• 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	None	None	1.0	N	0.699	0.246	0.0986583533028	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.9215	likely_pathogenic	0.9291	pathogenic	-0.67	Destabilizing	0.999	D	0.579	neutral	None	None	None	None	N
K/C	0.9552	likely_pathogenic	0.961	pathogenic	-0.554	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
K/D	0.9332	likely_pathogenic	0.9394	pathogenic	-0.206	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
K/E	0.8022	likely_pathogenic	0.8222	pathogenic	-0.091	Destabilizing	0.999	D	0.479	neutral	N	0.456190829	None	None	N
K/F	0.9721	likely_pathogenic	0.9758	pathogenic	-0.383	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
K/G	0.9512	likely_pathogenic	0.9569	pathogenic	-1.044	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
K/H	0.6731	likely_pathogenic	0.6817	pathogenic	-1.447	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
K/I	0.7774	likely_pathogenic	0.8012	pathogenic	0.302	Stabilizing	1.0	D	0.697	prob.neutral	N	0.450174381	None	None	N
K/L	0.8019	likely_pathogenic	0.8132	pathogenic	0.302	Stabilizing	1.0	D	0.663	neutral	None	None	None	None	N
K/M	0.7001	likely_pathogenic	0.7203	pathogenic	0.26	Stabilizing	1.0	D	0.663	neutral	None	None	None	None	N
K/N	0.8041	likely_pathogenic	0.8154	pathogenic	-0.555	Destabilizing	1.0	D	0.699	prob.neutral	N	0.455012854	None	None	N
K/P	0.9633	likely_pathogenic	0.9691	pathogenic	0.008	Stabilizing	1.0	D	0.663	neutral	None	None	None	None	N
K/Q	0.5561	ambiguous	0.5744	pathogenic	-0.599	Destabilizing	1.0	D	0.673	neutral	N	0.450174381	None	None	N
K/R	0.1437	likely_benign	0.1451	benign	-0.724	Destabilizing	0.999	D	0.493	neutral	N	0.362883062	None	None	N
K/S	0.913	likely_pathogenic	0.9211	pathogenic	-1.199	Destabilizing	0.999	D	0.582	neutral	None	None	None	None	N
K/T	0.6912	likely_pathogenic	0.7161	pathogenic	-0.871	Destabilizing	1.0	D	0.691	prob.neutral	N	0.456848273	None	None	N
K/V	0.8049	likely_pathogenic	0.8253	pathogenic	0.008	Stabilizing	1.0	D	0.673	neutral	None	None	None	None	N
K/W	0.9628	likely_pathogenic	0.9684	pathogenic	-0.273	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
K/Y	0.921	likely_pathogenic	0.9295	pathogenic	0.015	Stabilizing	1.0	D	0.665	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.