TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32365	97318;97319;97320	chr2:178542761;178542760;178542759	chr2:179407488;179407487;179407486
N2AB	30724	92395;92396;92397	chr2:178542761;178542760;178542759	chr2:179407488;179407487;179407486
N2A	29797	89614;89615;89616	chr2:178542761;178542760;178542759	chr2:179407488;179407487;179407486
N2B	23300	70123;70124;70125	chr2:178542761;178542760;178542759	chr2:179407488;179407487;179407486
Novex-1	23425	70498;70499;70500	chr2:178542761;178542760;178542759	chr2:179407488;179407487;179407486
Novex-2	23492	70699;70700;70701	chr2:178542761;178542760;178542759	chr2:179407488;179407487;179407486
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-154
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.2095
• 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
T/I	None	None	0.028	N	0.481	0.275	0.424194796918	gnomAD-4.0.0	1.59123E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85829E-06	0	0
T/S	None	None	0.028	N	0.463	0.157	0.247322355667	gnomAD-4.0.0	3.18246E-06	None	None	None	None	N	None	0	0	None	0	2.77285E-05	None	0	0	2.85829E-06	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
T/A	0.0973	likely_benign	0.0862	benign	-1.212	Destabilizing	0.309	N	0.587	neutral	D	0.534177052	None	None	N
T/C	0.3245	likely_benign	0.2865	benign	-1.239	Destabilizing	0.996	D	0.673	neutral	None	None	None	None	N
T/D	0.5439	ambiguous	0.4892	ambiguous	-1.874	Destabilizing	0.91	D	0.68	prob.neutral	None	None	None	None	N
T/E	0.4202	ambiguous	0.3783	ambiguous	-1.726	Destabilizing	0.91	D	0.683	prob.neutral	None	None	None	None	N
T/F	0.1943	likely_benign	0.1722	benign	-0.807	Destabilizing	0.953	D	0.674	neutral	None	None	None	None	N
T/G	0.2842	likely_benign	0.2551	benign	-1.571	Destabilizing	0.59	D	0.664	neutral	None	None	None	None	N
T/H	0.2114	likely_benign	0.1935	benign	-1.625	Destabilizing	0.996	D	0.673	neutral	None	None	None	None	N
T/I	0.127	likely_benign	0.1165	benign	-0.292	Destabilizing	0.028	N	0.481	neutral	N	0.494869302	None	None	N
T/K	0.2349	likely_benign	0.2197	benign	-1.041	Destabilizing	0.91	D	0.683	prob.neutral	None	None	None	None	N
T/L	0.0925	likely_benign	0.0847	benign	-0.292	Destabilizing	0.373	N	0.624	neutral	None	None	None	None	N
T/M	0.0869	likely_benign	0.0842	benign	-0.351	Destabilizing	0.953	D	0.693	prob.neutral	None	None	None	None	N
T/N	0.1404	likely_benign	0.1286	benign	-1.551	Destabilizing	0.884	D	0.663	neutral	D	0.534870485	None	None	N
T/P	0.7286	likely_pathogenic	0.691	pathogenic	-0.569	Destabilizing	0.939	D	0.693	prob.neutral	N	0.511273139	None	None	N
T/Q	0.2268	likely_benign	0.2137	benign	-1.488	Destabilizing	0.91	D	0.711	prob.delet.	None	None	None	None	N
T/R	0.1805	likely_benign	0.1622	benign	-0.993	Destabilizing	0.91	D	0.706	prob.neutral	None	None	None	None	N
T/S	0.1198	likely_benign	0.1087	benign	-1.71	Destabilizing	0.028	N	0.463	neutral	N	0.504547578	None	None	N
T/V	0.1184	likely_benign	0.1077	benign	-0.569	Destabilizing	0.016	N	0.281	neutral	None	None	None	None	N
T/W	0.4744	ambiguous	0.4395	ambiguous	-0.907	Destabilizing	0.996	D	0.699	prob.neutral	None	None	None	None	N
T/Y	0.2278	likely_benign	0.2055	benign	-0.588	Destabilizing	0.984	D	0.674	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.