TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6640	20143;20144;20145	chr2:178727660;178727659;178727658	chr2:179592387;179592386;179592385
N2AB	6323	19192;19193;19194	chr2:178727660;178727659;178727658	chr2:179592387;179592386;179592385
N2A	5396	16411;16412;16413	chr2:178727660;178727659;178727658	chr2:179592387;179592386;179592385
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-50
• Domain position: 67
• Structural Position: 149
• Q(SASA): 0.2136
• 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	0.27	N	0.545	0.192	0.303123707472	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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	0.2786	likely_benign	0.2934	benign	-0.972	Destabilizing	0.329	N	0.569	neutral	None	None	None	None	N
K/C	0.6389	likely_pathogenic	0.669	pathogenic	-0.977	Destabilizing	0.995	D	0.775	deleterious	None	None	None	None	N
K/D	0.4594	ambiguous	0.4987	ambiguous	-0.287	Destabilizing	0.704	D	0.667	neutral	None	None	None	None	N
K/E	0.1375	likely_benign	0.1546	benign	-0.127	Destabilizing	0.27	N	0.545	neutral	N	0.402879074	None	None	N
K/F	0.7652	likely_pathogenic	0.7784	pathogenic	-0.699	Destabilizing	0.944	D	0.795	deleterious	None	None	None	None	N
K/G	0.3604	ambiguous	0.3718	ambiguous	-1.348	Destabilizing	0.543	D	0.681	prob.neutral	None	None	None	None	N
K/H	0.2831	likely_benign	0.2973	benign	-1.484	Destabilizing	0.007	N	0.45	neutral	None	None	None	None	N
K/I	0.4138	ambiguous	0.4424	ambiguous	0.02	Stabilizing	0.944	D	0.79	deleterious	None	None	None	None	N
K/L	0.3389	likely_benign	0.3638	ambiguous	0.02	Stabilizing	0.704	D	0.723	prob.delet.	None	None	None	None	N
K/M	0.2088	likely_benign	0.2341	benign	-0.143	Destabilizing	0.975	D	0.721	prob.delet.	N	0.417272523	None	None	N
K/N	0.3364	likely_benign	0.3591	ambiguous	-0.861	Destabilizing	0.642	D	0.587	neutral	N	0.402705716	None	None	N
K/P	0.8341	likely_pathogenic	0.8312	pathogenic	-0.283	Destabilizing	0.944	D	0.728	prob.delet.	None	None	None	None	N
K/Q	0.1049	likely_benign	0.1096	benign	-0.785	Destabilizing	0.065	N	0.352	neutral	N	0.327517311	None	None	N
K/R	0.0817	likely_benign	0.078	benign	-0.66	Destabilizing	0.006	N	0.335	neutral	N	0.441706821	None	None	N
K/S	0.302	likely_benign	0.3263	benign	-1.568	Destabilizing	0.031	N	0.346	neutral	None	None	None	None	N
K/T	0.1588	likely_benign	0.1729	benign	-1.169	Destabilizing	0.473	N	0.658	neutral	N	0.441706821	None	None	N
K/V	0.3153	likely_benign	0.3382	benign	-0.283	Destabilizing	0.704	D	0.735	prob.delet.	None	None	None	None	N
K/W	0.7318	likely_pathogenic	0.753	pathogenic	-0.571	Destabilizing	0.995	D	0.775	deleterious	None	None	None	None	N
K/Y	0.5474	ambiguous	0.5824	pathogenic	-0.295	Destabilizing	0.893	D	0.767	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.