TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22046	66361;66362;66363	chr2:178582320;178582319;178582318	chr2:179447047;179447046;179447045
N2AB	20405	61438;61439;61440	chr2:178582320;178582319;178582318	chr2:179447047;179447046;179447045
N2A	19478	58657;58658;58659	chr2:178582320;178582319;178582318	chr2:179447047;179447046;179447045
N2B	12981	39166;39167;39168	chr2:178582320;178582319;178582318	chr2:179447047;179447046;179447045
Novex-1	13106	39541;39542;39543	chr2:178582320;178582319;178582318	chr2:179447047;179447046;179447045
Novex-2	13173	39742;39743;39744	chr2:178582320;178582319;178582318	chr2:179447047;179447046;179447045
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-47
• Domain position: 91
• Structural Position: 126
• Q(SASA): 0.4685
• 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
P/L	None	None	0.666	D	0.723	0.465	0.595302103986	gnomAD-4.0.0	6.96131E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.07406E-07	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
P/A	0.0788	likely_benign	0.0651	benign	-0.739	Destabilizing	0.051	N	0.317	neutral	N	0.491676583	None	None	N
P/C	0.6353	likely_pathogenic	0.5365	ambiguous	-0.573	Destabilizing	0.998	D	0.815	deleterious	None	None	None	None	N
P/D	0.716	likely_pathogenic	0.6264	pathogenic	-0.69	Destabilizing	0.841	D	0.621	neutral	None	None	None	None	N
P/E	0.5195	ambiguous	0.4286	ambiguous	-0.803	Destabilizing	0.841	D	0.603	neutral	None	None	None	None	N
P/F	0.7894	likely_pathogenic	0.7237	pathogenic	-0.899	Destabilizing	0.974	D	0.823	deleterious	None	None	None	None	N
P/G	0.4613	ambiguous	0.359	ambiguous	-0.902	Destabilizing	0.725	D	0.65	prob.neutral	None	None	None	None	N
P/H	0.4758	ambiguous	0.3721	ambiguous	-0.438	Destabilizing	0.998	D	0.758	deleterious	None	None	None	None	N
P/I	0.4787	ambiguous	0.434	ambiguous	-0.451	Destabilizing	0.949	D	0.776	deleterious	None	None	None	None	N
P/K	0.5628	ambiguous	0.4511	ambiguous	-0.644	Destabilizing	0.841	D	0.599	neutral	None	None	None	None	N
P/L	0.2846	likely_benign	0.2467	benign	-0.451	Destabilizing	0.666	D	0.723	deleterious	D	0.52768451	None	None	N
P/M	0.472	ambiguous	0.4174	ambiguous	-0.337	Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	N
P/N	0.5353	ambiguous	0.4629	ambiguous	-0.314	Destabilizing	0.949	D	0.674	prob.neutral	None	None	None	None	N
P/Q	0.3875	ambiguous	0.3043	benign	-0.617	Destabilizing	0.966	D	0.681	prob.neutral	N	0.494830135	None	None	N
P/R	0.4808	ambiguous	0.374	ambiguous	-0.025	Destabilizing	0.933	D	0.725	deleterious	N	0.509073276	None	None	N
P/S	0.2066	likely_benign	0.1574	benign	-0.665	Destabilizing	0.051	N	0.323	neutral	N	0.487802243	None	None	N
P/T	0.1532	likely_benign	0.138	benign	-0.685	Destabilizing	0.051	N	0.313	neutral	N	0.48361196	None	None	N
P/V	0.2952	likely_benign	0.2662	benign	-0.512	Destabilizing	0.725	D	0.657	prob.neutral	None	None	None	None	N
P/W	0.8982	likely_pathogenic	0.8488	pathogenic	-0.969	Destabilizing	0.998	D	0.782	deleterious	None	None	None	None	N
P/Y	0.7548	likely_pathogenic	0.6631	pathogenic	-0.685	Destabilizing	0.991	D	0.822	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.