TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8580	25963;25964;25965	chr2:178715676;178715675;178715674	chr2:179580403;179580402;179580401
N2AB	8263	25012;25013;25014	chr2:178715676;178715675;178715674	chr2:179580403;179580402;179580401
N2A	7336	22231;22232;22233	chr2:178715676;178715675;178715674	chr2:179580403;179580402;179580401
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-71
• Domain position: 32
• Structural Position: 45
• Q(SASA): 0.4354
• Predicted PPI site: I

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
K/R	None	None	None	N	0.134	0.103	0.267299060538	gnomAD-4.0.0	1.59385E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43674E-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
K/A	0.2534	likely_benign	0.256	benign	-0.252	Destabilizing	0.359	N	0.486	neutral	None	None	None	None	I
K/C	0.6706	likely_pathogenic	0.6738	pathogenic	-0.332	Destabilizing	0.996	D	0.587	neutral	None	None	None	None	I
K/D	0.3849	ambiguous	0.3804	ambiguous	-0.129	Destabilizing	0.576	D	0.516	neutral	None	None	None	None	I
K/E	0.1112	likely_benign	0.1125	benign	-0.035	Destabilizing	0.202	N	0.472	neutral	N	0.490055341	None	None	I
K/F	0.6752	likely_pathogenic	0.6856	pathogenic	0.039	Stabilizing	0.959	D	0.596	neutral	None	None	None	None	I
K/G	0.3908	ambiguous	0.3937	ambiguous	-0.582	Destabilizing	0.576	D	0.548	neutral	None	None	None	None	I
K/H	0.1951	likely_benign	0.2002	benign	-0.837	Destabilizing	0.889	D	0.556	neutral	None	None	None	None	I
K/I	0.288	likely_benign	0.3011	benign	0.584	Stabilizing	0.3	N	0.609	neutral	N	0.518591524	None	None	I
K/L	0.2895	likely_benign	0.2971	benign	0.584	Stabilizing	0.074	N	0.557	neutral	None	None	None	None	I
K/M	0.1949	likely_benign	0.2011	benign	0.19	Stabilizing	0.875	D	0.541	neutral	None	None	None	None	I
K/N	0.2581	likely_benign	0.2495	benign	-0.253	Destabilizing	0.006	N	0.321	neutral	N	0.510086684	None	None	I
K/P	0.8144	likely_pathogenic	0.7962	pathogenic	0.335	Stabilizing	0.951	D	0.582	neutral	None	None	None	None	I
K/Q	0.0963	likely_benign	0.1	benign	-0.265	Destabilizing	0.198	N	0.499	neutral	N	0.496117309	None	None	I
K/R	0.0754	likely_benign	0.0767	benign	-0.472	Destabilizing	None	N	0.134	neutral	N	0.484862952	None	None	I
K/S	0.2537	likely_benign	0.2547	benign	-0.732	Destabilizing	0.095	N	0.198	neutral	None	None	None	None	I
K/T	0.1043	likely_benign	0.1083	benign	-0.451	Destabilizing	0.235	N	0.519	neutral	N	0.487401825	None	None	I
K/V	0.2517	likely_benign	0.2606	benign	0.335	Stabilizing	0.427	N	0.603	neutral	None	None	None	None	I
K/W	0.6199	likely_pathogenic	0.648	pathogenic	0.051	Stabilizing	0.997	D	0.639	neutral	None	None	None	None	I
K/Y	0.5346	ambiguous	0.5423	ambiguous	0.329	Stabilizing	0.732	D	0.605	neutral	None	None	None	None	I

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.