TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8478	25657;25658;25659	chr2:178717302;178717301;178717300	chr2:179582029;179582028;179582027
N2AB	8161	24706;24707;24708	chr2:178717302;178717301;178717300	chr2:179582029;179582028;179582027
N2A	7234	21925;21926;21927	chr2:178717302;178717301;178717300	chr2:179582029;179582028;179582027
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: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-70
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.2394
• 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/Q	None	None	0.993	N	0.531	0.23	0.218845423259	gnomAD-4.0.0	6.84279E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99557E-07	0	0
H/R	rs747367057	-0.865	0.949	N	0.502	0.247	0.250579442822	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
H/R	rs747367057	-0.865	0.949	N	0.502	0.247	0.250579442822	gnomAD-4.0.0	1.59165E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4332E-05	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
H/A	0.857	likely_pathogenic	0.8424	pathogenic	-0.864	Destabilizing	0.981	D	0.533	neutral	None	None	None	None	N
H/C	0.6069	likely_pathogenic	0.5801	pathogenic	-0.3	Destabilizing	1.0	D	0.613	neutral	None	None	None	None	N
H/D	0.8481	likely_pathogenic	0.8404	pathogenic	-0.759	Destabilizing	0.983	D	0.545	neutral	N	0.487265752	None	None	N
H/E	0.814	likely_pathogenic	0.7895	pathogenic	-0.686	Destabilizing	0.981	D	0.491	neutral	None	None	None	None	N
H/F	0.7445	likely_pathogenic	0.7413	pathogenic	-0.09	Destabilizing	0.992	D	0.546	neutral	None	None	None	None	N
H/G	0.8913	likely_pathogenic	0.8694	pathogenic	-1.183	Destabilizing	0.996	D	0.544	neutral	None	None	None	None	N
H/I	0.8527	likely_pathogenic	0.8584	pathogenic	0.002	Stabilizing	0.961	D	0.589	neutral	None	None	None	None	N
H/K	0.6043	likely_pathogenic	0.5495	ambiguous	-0.828	Destabilizing	0.396	N	0.326	neutral	None	None	None	None	N
H/L	0.4908	ambiguous	0.5158	ambiguous	0.002	Stabilizing	0.949	D	0.571	neutral	N	0.510662687	None	None	N
H/M	0.8868	likely_pathogenic	0.8901	pathogenic	-0.082	Destabilizing	0.997	D	0.594	neutral	None	None	None	None	N
H/N	0.4605	ambiguous	0.4783	ambiguous	-0.773	Destabilizing	0.983	D	0.493	neutral	N	0.510969331	None	None	N
H/P	0.9115	likely_pathogenic	0.9136	pathogenic	-0.267	Destabilizing	0.998	D	0.589	neutral	N	0.513086917	None	None	N
H/Q	0.5468	ambiguous	0.506	ambiguous	-0.586	Destabilizing	0.993	D	0.531	neutral	N	0.491420778	None	None	N
H/R	0.1999	likely_benign	0.1758	benign	-1.062	Destabilizing	0.949	D	0.502	neutral	N	0.436991648	None	None	N
H/S	0.7522	likely_pathogenic	0.7375	pathogenic	-0.865	Destabilizing	0.992	D	0.491	neutral	None	None	None	None	N
H/T	0.8259	likely_pathogenic	0.8075	pathogenic	-0.702	Destabilizing	0.974	D	0.559	neutral	None	None	None	None	N
H/V	0.7822	likely_pathogenic	0.7798	pathogenic	-0.267	Destabilizing	0.406	N	0.503	neutral	None	None	None	None	N
H/W	0.7543	likely_pathogenic	0.7359	pathogenic	0.032	Stabilizing	1.0	D	0.594	neutral	None	None	None	None	N
H/Y	0.3401	ambiguous	0.3466	ambiguous	0.302	Stabilizing	0.409	N	0.311	neutral	N	0.497062315	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.