TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22658	68197;68198;68199	chr2:178579058;178579057;178579056	chr2:179443785;179443784;179443783
N2AB	21017	63274;63275;63276	chr2:178579058;178579057;178579056	chr2:179443785;179443784;179443783
N2A	20090	60493;60494;60495	chr2:178579058;178579057;178579056	chr2:179443785;179443784;179443783
N2B	13593	41002;41003;41004	chr2:178579058;178579057;178579056	chr2:179443785;179443784;179443783
Novex-1	13718	41377;41378;41379	chr2:178579058;178579057;178579056	chr2:179443785;179443784;179443783
Novex-2	13785	41578;41579;41580	chr2:178579058;178579057;178579056	chr2:179443785;179443784;179443783
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-52
• Domain position: 16
• Structural Position: 17
• Q(SASA): 0.2351
• 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
A/T	None	None	1.0	N	0.761	0.378	0.406806705197	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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
A/C	0.5582	ambiguous	0.5627	ambiguous	-0.953	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
A/D	0.7598	likely_pathogenic	0.7902	pathogenic	-1.985	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
A/E	0.6422	likely_pathogenic	0.6496	pathogenic	-2.068	Highly Destabilizing	1.0	D	0.79	deleterious	N	0.493140427	None	None	N
A/F	0.727	likely_pathogenic	0.7114	pathogenic	-1.313	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
A/G	0.2259	likely_benign	0.2374	benign	-1.137	Destabilizing	1.0	D	0.539	neutral	N	0.46947692	None	None	N
A/H	0.7882	likely_pathogenic	0.7973	pathogenic	-1.198	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
A/I	0.5243	ambiguous	0.4917	ambiguous	-0.604	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
A/K	0.751	likely_pathogenic	0.7404	pathogenic	-1.226	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
A/L	0.4742	ambiguous	0.4494	ambiguous	-0.604	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
A/M	0.4602	ambiguous	0.4372	ambiguous	-0.32	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
A/N	0.5789	likely_pathogenic	0.6073	pathogenic	-0.986	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
A/P	0.436	ambiguous	0.4477	ambiguous	-0.684	Destabilizing	1.0	D	0.799	deleterious	N	0.49383386	None	None	N
A/Q	0.6358	likely_pathogenic	0.635	pathogenic	-1.3	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
A/R	0.6691	likely_pathogenic	0.6703	pathogenic	-0.711	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
A/S	0.112	likely_benign	0.118	benign	-1.175	Destabilizing	1.0	D	0.549	neutral	N	0.472013006	None	None	N
A/T	0.2021	likely_benign	0.1963	benign	-1.195	Destabilizing	1.0	D	0.761	deleterious	N	0.467165276	None	None	N
A/V	0.2511	likely_benign	0.2451	benign	-0.684	Destabilizing	1.0	D	0.683	prob.neutral	N	0.479664125	None	None	N
A/W	0.9315	likely_pathogenic	0.9257	pathogenic	-1.574	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
A/Y	0.8133	likely_pathogenic	0.801	pathogenic	-1.219	Destabilizing	1.0	D	0.789	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.