TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5079	15460;15461;15462	chr2:178734589;178734588;178734587	chr2:179599316;179599315;179599314
N2AB	4762	14509;14510;14511	chr2:178734589;178734588;178734587	chr2:179599316;179599315;179599314
N2A	3835	11728;11729;11730	chr2:178734589;178734588;178734587	chr2:179599316;179599315;179599314
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: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-34
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.6021
• 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	rs1327420984	None	0.124	D	0.457	0.189	0.29132392195	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/E	rs1327420984	None	0.124	D	0.457	0.189	0.29132392195	gnomAD-4.0.0	6.57056E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.46998E-05	0	0
K/R	None	None	0.001	N	0.174	0.066	0.178374595973	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.381	ambiguous	0.3572	ambiguous	-0.399	Destabilizing	0.272	N	0.445	neutral	None	None	None	None	I
K/C	0.6576	likely_pathogenic	0.6565	pathogenic	-0.389	Destabilizing	0.968	D	0.638	neutral	None	None	None	None	I
K/D	0.6075	likely_pathogenic	0.5535	ambiguous	-0.036	Destabilizing	0.396	N	0.414	neutral	None	None	None	None	I
K/E	0.1792	likely_benign	0.168	benign	0.068	Stabilizing	0.124	N	0.457	neutral	D	0.560652647	None	None	I
K/F	0.8092	likely_pathogenic	0.7944	pathogenic	0.025	Stabilizing	0.726	D	0.599	neutral	None	None	None	None	I
K/G	0.4364	ambiguous	0.4078	ambiguous	-0.766	Destabilizing	0.272	N	0.473	neutral	None	None	None	None	I
K/H	0.2537	likely_benign	0.2266	benign	-1.056	Destabilizing	0.726	D	0.485	neutral	None	None	None	None	I
K/I	0.4819	ambiguous	0.4772	ambiguous	0.547	Stabilizing	0.667	D	0.607	neutral	D	0.561832602	None	None	I
K/L	0.4315	ambiguous	0.4125	ambiguous	0.547	Stabilizing	0.272	N	0.447	neutral	None	None	None	None	I
K/M	0.3166	likely_benign	0.2957	benign	0.32	Stabilizing	0.968	D	0.496	neutral	None	None	None	None	I
K/N	0.4076	ambiguous	0.3522	ambiguous	-0.328	Destabilizing	0.009	N	0.176	neutral	N	0.509387618	None	None	I
K/P	0.9145	likely_pathogenic	0.9068	pathogenic	0.262	Stabilizing	0.726	D	0.466	neutral	None	None	None	None	I
K/Q	0.1148	likely_benign	0.1055	benign	-0.373	Destabilizing	0.497	N	0.424	neutral	N	0.486659458	None	None	I
K/R	0.0686	likely_benign	0.0709	benign	-0.619	Destabilizing	0.001	N	0.174	neutral	N	0.484484248	None	None	I
K/S	0.3857	ambiguous	0.3408	ambiguous	-0.928	Destabilizing	0.272	N	0.399	neutral	None	None	None	None	I
K/T	0.2019	likely_benign	0.1759	benign	-0.626	Destabilizing	0.22	N	0.426	neutral	N	0.50662802	None	None	I
K/V	0.4168	ambiguous	0.4079	ambiguous	0.262	Stabilizing	0.567	D	0.55	neutral	None	None	None	None	I
K/W	0.7123	likely_pathogenic	0.7196	pathogenic	0.123	Stabilizing	0.968	D	0.66	neutral	None	None	None	None	I
K/Y	0.6313	likely_pathogenic	0.6245	pathogenic	0.377	Stabilizing	0.726	D	0.569	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.