TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8933	27022;27023;27024	chr2:178713337;178713336;178713335	chr2:179578064;179578063;179578062
N2AB	8616	26071;26072;26073	chr2:178713337;178713336;178713335	chr2:179578064;179578063;179578062
N2A	7689	23290;23291;23292	chr2:178713337;178713336;178713335	chr2:179578064;179578063;179578062
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-75
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.7441
• 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/E	None	None	0.978	N	0.577	0.399	0.473458370588	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	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	0.4119	ambiguous	0.5541	ambiguous	0.016	Stabilizing	0.983	D	0.573	neutral	None	None	None	None	N
K/C	0.7842	likely_pathogenic	0.8435	pathogenic	-0.442	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
K/D	0.7055	likely_pathogenic	0.8325	pathogenic	-0.308	Destabilizing	0.998	D	0.599	neutral	None	None	None	None	N
K/E	0.2014	likely_benign	0.338	benign	-0.318	Destabilizing	0.978	D	0.577	neutral	N	0.504662221	None	None	N
K/F	0.8057	likely_pathogenic	0.8866	pathogenic	-0.286	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
K/G	0.4666	ambiguous	0.5961	pathogenic	-0.126	Destabilizing	0.992	D	0.545	neutral	None	None	None	None	N
K/H	0.3714	ambiguous	0.4339	ambiguous	-0.23	Destabilizing	1.0	D	0.642	neutral	None	None	None	None	N
K/I	0.4587	ambiguous	0.6173	pathogenic	0.305	Stabilizing	0.994	D	0.687	prob.neutral	N	0.503448779	None	None	N
K/L	0.4024	ambiguous	0.5643	pathogenic	0.305	Stabilizing	0.983	D	0.542	neutral	None	None	None	None	N
K/M	0.2988	likely_benign	0.4347	ambiguous	-0.066	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	N
K/N	0.5545	ambiguous	0.7271	pathogenic	-0.014	Destabilizing	0.997	D	0.581	neutral	N	0.504624936	None	None	N
K/P	0.7592	likely_pathogenic	0.8216	pathogenic	0.232	Stabilizing	0.999	D	0.663	neutral	None	None	None	None	N
K/Q	0.1435	likely_benign	0.1907	benign	-0.163	Destabilizing	0.994	D	0.607	neutral	N	0.478534413	None	None	N
K/R	0.0776	likely_benign	0.076	benign	-0.129	Destabilizing	0.241	N	0.291	neutral	N	0.502160634	None	None	N
K/S	0.4924	ambiguous	0.6506	pathogenic	-0.376	Destabilizing	0.967	D	0.566	neutral	None	None	None	None	N
K/T	0.2326	likely_benign	0.3475	ambiguous	-0.267	Destabilizing	0.576	D	0.349	neutral	N	0.47347531	None	None	N
K/V	0.4168	ambiguous	0.5657	pathogenic	0.232	Stabilizing	0.995	D	0.523	neutral	None	None	None	None	N
K/W	0.7243	likely_pathogenic	0.7692	pathogenic	-0.377	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
K/Y	0.7012	likely_pathogenic	0.7853	pathogenic	-0.029	Destabilizing	0.999	D	0.671	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.