TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16893	50902;50903;50904	chr2:178611552;178611551;178611550	chr2:179476279;179476278;179476277
N2AB	15252	45979;45980;45981	chr2:178611552;178611551;178611550	chr2:179476279;179476278;179476277
N2A	14325	43198;43199;43200	chr2:178611552;178611551;178611550	chr2:179476279;179476278;179476277
N2B	7828	23707;23708;23709	chr2:178611552;178611551;178611550	chr2:179476279;179476278;179476277
Novex-1	7953	24082;24083;24084	chr2:178611552;178611551;178611550	chr2:179476279;179476278;179476277
Novex-2	8020	24283;24284;24285	chr2:178611552;178611551;178611550	chr2:179476279;179476278;179476277
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: Fn3-11
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.2609
• 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/A	None	None	0.051	N	0.203	0.186	0.16115917748	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
P/A	0.0837	likely_benign	0.0855	benign	-1.861	Destabilizing	0.051	N	0.203	neutral	N	0.451021006	None	None	N
P/C	0.7038	likely_pathogenic	0.7167	pathogenic	-1.106	Destabilizing	0.998	D	0.55	neutral	None	None	None	None	N
P/D	0.6749	likely_pathogenic	0.6163	pathogenic	-2.135	Highly Destabilizing	0.728	D	0.428	neutral	None	None	None	None	N
P/E	0.2919	likely_benign	0.2582	benign	-2.067	Highly Destabilizing	0.007	N	0.18	neutral	None	None	None	None	N
P/F	0.738	likely_pathogenic	0.7226	pathogenic	-1.351	Destabilizing	0.991	D	0.553	neutral	None	None	None	None	N
P/G	0.5118	ambiguous	0.4878	ambiguous	-2.263	Highly Destabilizing	0.842	D	0.457	neutral	None	None	None	None	N
P/H	0.3608	ambiguous	0.3317	benign	-1.994	Destabilizing	0.974	D	0.509	neutral	None	None	None	None	N
P/I	0.431	ambiguous	0.436	ambiguous	-0.809	Destabilizing	0.974	D	0.557	neutral	None	None	None	None	N
P/K	0.5489	ambiguous	0.4737	ambiguous	-1.612	Destabilizing	0.728	D	0.432	neutral	None	None	None	None	N
P/L	0.156	likely_benign	0.152	benign	-0.809	Destabilizing	0.801	D	0.499	neutral	N	0.465157423	None	None	N
P/M	0.3747	ambiguous	0.393	ambiguous	-0.5	Destabilizing	0.998	D	0.497	neutral	None	None	None	None	N
P/N	0.5232	ambiguous	0.5119	ambiguous	-1.491	Destabilizing	0.949	D	0.491	neutral	None	None	None	None	N
P/Q	0.1986	likely_benign	0.1887	benign	-1.571	Destabilizing	0.669	D	0.443	neutral	N	0.437244903	None	None	N
P/R	0.379	ambiguous	0.3309	benign	-1.16	Destabilizing	0.934	D	0.493	neutral	N	0.443901003	None	None	N
P/S	0.1735	likely_benign	0.1719	benign	-2.004	Highly Destabilizing	0.669	D	0.422	neutral	N	0.445119111	None	None	N
P/T	0.1318	likely_benign	0.1332	benign	-1.825	Destabilizing	0.801	D	0.419	neutral	N	0.437970399	None	None	N
P/V	0.2691	likely_benign	0.2773	benign	-1.128	Destabilizing	0.842	D	0.476	neutral	None	None	None	None	N
P/W	0.8766	likely_pathogenic	0.8615	pathogenic	-1.732	Destabilizing	0.998	D	0.614	neutral	None	None	None	None	N
P/Y	0.7341	likely_pathogenic	0.7115	pathogenic	-1.417	Destabilizing	0.991	D	0.56	neutral	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.