TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19096	57511;57512;57513	chr2:178597796;178597795;178597794	chr2:179462523;179462522;179462521
N2AB	17455	52588;52589;52590	chr2:178597796;178597795;178597794	chr2:179462523;179462522;179462521
N2A	16528	49807;49808;49809	chr2:178597796;178597795;178597794	chr2:179462523;179462522;179462521
N2B	10031	30316;30317;30318	chr2:178597796;178597795;178597794	chr2:179462523;179462522;179462521
Novex-1	10156	30691;30692;30693	chr2:178597796;178597795;178597794	chr2:179462523;179462522;179462521
Novex-2	10223	30892;30893;30894	chr2:178597796;178597795;178597794	chr2:179462523;179462522;179462521
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-117
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.4306
• 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/V	rs1559650624	-0.062	0.998	N	0.636	0.39	0.365509141856	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	5.82E-05	None	0	0	None	0	None	0	0	0
A/V	rs1559650624	-0.062	0.998	N	0.636	0.39	0.365509141856	gnomAD-4.0.0	3.1855E-06	None	None	None	None	N	None	0	4.5798E-05	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
A/C	0.7958	likely_pathogenic	0.7825	pathogenic	-0.946	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
A/D	0.8877	likely_pathogenic	0.9194	pathogenic	-0.57	Destabilizing	0.999	D	0.736	prob.delet.	N	0.500789623	None	None	N
A/E	0.8454	likely_pathogenic	0.8824	pathogenic	-0.708	Destabilizing	0.999	D	0.67	neutral	None	None	None	None	N
A/F	0.7444	likely_pathogenic	0.7741	pathogenic	-0.979	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
A/G	0.4451	ambiguous	0.4468	ambiguous	-0.346	Destabilizing	0.996	D	0.609	neutral	N	0.486321603	None	None	N
A/H	0.888	likely_pathogenic	0.9048	pathogenic	-0.25	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
A/I	0.4984	ambiguous	0.5575	ambiguous	-0.524	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
A/K	0.9408	likely_pathogenic	0.9538	pathogenic	-0.641	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
A/L	0.4112	ambiguous	0.4868	ambiguous	-0.524	Destabilizing	0.998	D	0.635	neutral	None	None	None	None	N
A/M	0.5218	ambiguous	0.5991	pathogenic	-0.724	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
A/N	0.681	likely_pathogenic	0.7541	pathogenic	-0.369	Destabilizing	0.999	D	0.73	prob.delet.	None	None	None	None	N
A/P	0.599	likely_pathogenic	0.6453	pathogenic	-0.442	Destabilizing	0.999	D	0.677	prob.neutral	N	0.50123234	None	None	N
A/Q	0.7805	likely_pathogenic	0.8246	pathogenic	-0.604	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
A/R	0.9012	likely_pathogenic	0.9132	pathogenic	-0.215	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
A/S	0.1983	likely_benign	0.2153	benign	-0.574	Destabilizing	0.957	D	0.42	neutral	N	0.481779788	None	None	N
A/T	0.2805	likely_benign	0.3417	ambiguous	-0.64	Destabilizing	0.992	D	0.628	neutral	N	0.500616265	None	None	N
A/V	0.2633	likely_benign	0.324	benign	-0.442	Destabilizing	0.998	D	0.636	neutral	N	0.44874465	None	None	N
A/W	0.9663	likely_pathogenic	0.9666	pathogenic	-1.056	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
A/Y	0.865	likely_pathogenic	0.8717	pathogenic	-0.775	Destabilizing	1.0	D	0.766	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.