TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7485	22678;22679;22680	chr2:178722334;178722333;178722332	chr2:179587061;179587060;179587059
N2AB	7168	21727;21728;21729	chr2:178722334;178722333;178722332	chr2:179587061;179587060;179587059
N2A	6241	18946;18947;18948	chr2:178722334;178722333;178722332	chr2:179587061;179587060;179587059
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: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-59
• Domain position: 67
• Structural Position: 149
• Q(SASA): 0.1473
• 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
H/N	rs1372592118	None	0.352	D	0.305	0.234	0.236278675362	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92976E-04	None	0	0	0	0	0
H/N	rs1372592118	None	0.352	D	0.305	0.234	0.236278675362	gnomAD-4.0.0	2.47982E-06	None	None	None	None	N	None	0	0	None	0	2.23015E-05	None	0	0	0	2.19746E-05	1.60236E-05

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
H/A	0.547	ambiguous	0.4857	ambiguous	-0.62	Destabilizing	0.997	D	0.708	prob.delet.	None	None	None	None	N
H/C	0.4104	ambiguous	0.3089	benign	-0.085	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
H/D	0.2471	likely_benign	0.2369	benign	-0.175	Destabilizing	0.041	N	0.447	neutral	N	0.350867733	None	None	N
H/E	0.5889	likely_pathogenic	0.5274	ambiguous	-0.093	Destabilizing	0.973	D	0.519	neutral	None	None	None	None	N
H/F	0.4221	ambiguous	0.3666	ambiguous	0.287	Stabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
H/G	0.6172	likely_pathogenic	0.5662	pathogenic	-0.972	Destabilizing	0.994	D	0.687	prob.neutral	None	None	None	None	N
H/I	0.5179	ambiguous	0.4681	ambiguous	0.332	Stabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
H/K	0.5864	likely_pathogenic	0.5091	ambiguous	-0.423	Destabilizing	0.994	D	0.666	neutral	None	None	None	None	N
H/L	0.1767	likely_benign	0.1597	benign	0.332	Stabilizing	0.996	D	0.779	deleterious	N	0.497872009	None	None	N
H/M	0.6439	likely_pathogenic	0.6009	pathogenic	0.143	Stabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
H/N	0.1415	likely_benign	0.1449	benign	-0.477	Destabilizing	0.352	N	0.305	neutral	D	0.524917277	None	None	N
H/P	0.6075	likely_pathogenic	0.609	pathogenic	0.037	Stabilizing	1.0	D	0.796	deleterious	N	0.520495715	None	None	N
H/Q	0.3462	ambiguous	0.307	benign	-0.286	Destabilizing	0.996	D	0.651	neutral	D	0.52766958	None	None	N
H/R	0.3026	likely_benign	0.2377	benign	-0.866	Destabilizing	0.996	D	0.639	neutral	N	0.520495715	None	None	N
H/S	0.3747	ambiguous	0.3466	ambiguous	-0.626	Destabilizing	0.994	D	0.64	neutral	None	None	None	None	N
H/T	0.557	ambiguous	0.5007	ambiguous	-0.425	Destabilizing	0.992	D	0.741	deleterious	None	None	None	None	N
H/V	0.4642	ambiguous	0.4076	ambiguous	0.037	Stabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
H/W	0.571	likely_pathogenic	0.5183	ambiguous	0.534	Stabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
H/Y	0.1329	likely_benign	0.1119	benign	0.711	Stabilizing	0.999	D	0.656	neutral	N	0.50239146	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.