TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7234	21925;21926;21927	chr2:178723307;178723306;178723305	chr2:179588034;179588033;179588032
N2AB	6917	20974;20975;20976	chr2:178723307;178723306;178723305	chr2:179588034;179588033;179588032
N2A	5990	18193;18194;18195	chr2:178723307;178723306;178723305	chr2:179588034;179588033;179588032
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: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-57
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.6951
• Predicted PPI site: I

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/E	rs1243074128	0.64	0.999	N	0.616	0.254	0.465464902746	gnomAD-2.1.1	4.07E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	9.02E-06	0
K/E	rs1243074128	0.64	0.999	N	0.616	0.254	0.465464902746	gnomAD-4.0.0	3.19281E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.73227E-06	0	0
K/R	rs2078749547	None	0.999	N	0.547	0.185	0.351180957027	gnomAD-4.0.0	1.59662E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86625E-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
K/A	0.6647	likely_pathogenic	0.6997	pathogenic	-0.364	Destabilizing	0.999	D	0.667	neutral	None	None	None	None	I
K/C	0.8475	likely_pathogenic	0.8496	pathogenic	-0.464	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	I
K/D	0.7746	likely_pathogenic	0.7972	pathogenic	0.367	Stabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	I
K/E	0.3089	likely_benign	0.3484	ambiguous	0.437	Stabilizing	0.999	D	0.616	neutral	N	0.488174772	None	None	I
K/F	0.9062	likely_pathogenic	0.9106	pathogenic	-0.239	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	I
K/G	0.6783	likely_pathogenic	0.7226	pathogenic	-0.662	Destabilizing	1.0	D	0.646	neutral	None	None	None	None	I
K/H	0.3964	ambiguous	0.4049	ambiguous	-0.893	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	I
K/I	0.667	likely_pathogenic	0.6739	pathogenic	0.375	Stabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
K/L	0.5932	likely_pathogenic	0.6157	pathogenic	0.375	Stabilizing	1.0	D	0.646	neutral	None	None	None	None	I
K/M	0.4957	ambiguous	0.5246	ambiguous	0.191	Stabilizing	1.0	D	0.641	neutral	N	0.503952077	None	None	I
K/N	0.6237	likely_pathogenic	0.6559	pathogenic	-0.078	Destabilizing	1.0	D	0.718	prob.delet.	N	0.493721407	None	None	I
K/P	0.9158	likely_pathogenic	0.91	pathogenic	0.159	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
K/Q	0.1778	likely_benign	0.195	benign	-0.199	Destabilizing	1.0	D	0.692	prob.neutral	N	0.480017563	None	None	I
K/R	0.1012	likely_benign	0.1027	benign	-0.273	Destabilizing	0.999	D	0.547	neutral	N	0.510662687	None	None	I
K/S	0.643	likely_pathogenic	0.6883	pathogenic	-0.775	Destabilizing	0.999	D	0.652	neutral	None	None	None	None	I
K/T	0.3828	ambiguous	0.4152	ambiguous	-0.515	Destabilizing	1.0	D	0.718	prob.delet.	N	0.493908763	None	None	I
K/V	0.6221	likely_pathogenic	0.6324	pathogenic	0.159	Stabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	I
K/W	0.876	likely_pathogenic	0.876	pathogenic	-0.115	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
K/Y	0.8032	likely_pathogenic	0.8099	pathogenic	0.184	Stabilizing	1.0	D	0.653	neutral	None	None	None	None	I

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.