TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31986	96181;96182;96183	chr2:178544273;178544272;178544271	chr2:179409000;179408999;179408998
N2AB	30345	91258;91259;91260	chr2:178544273;178544272;178544271	chr2:179409000;179408999;179408998
N2A	29418	88477;88478;88479	chr2:178544273;178544272;178544271	chr2:179409000;179408999;179408998
N2B	22921	68986;68987;68988	chr2:178544273;178544272;178544271	chr2:179409000;179408999;179408998
Novex-1	23046	69361;69362;69363	chr2:178544273;178544272;178544271	chr2:179409000;179408999;179408998
Novex-2	23113	69562;69563;69564	chr2:178544273;178544272;178544271	chr2:179409000;179408999;179408998
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-121
• Domain position: 78
• Structural Position: 109
• Q(SASA): 0.0561
• 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	None	None	1.0	N	0.652	0.419	0.497679007273	gnomAD-4.0.0	1.59134E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85861E-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
A/C	0.5064	ambiguous	0.4957	ambiguous	-1.313	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
A/D	0.9419	likely_pathogenic	0.9422	pathogenic	-2.723	Highly Destabilizing	1.0	D	0.807	deleterious	N	0.472649459	None	None	N
A/E	0.8758	likely_pathogenic	0.8708	pathogenic	-2.458	Highly Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
A/F	0.7221	likely_pathogenic	0.6991	pathogenic	-0.624	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
A/G	0.2043	likely_benign	0.2131	benign	-1.807	Destabilizing	1.0	D	0.605	neutral	N	0.473156438	None	None	N
A/H	0.8801	likely_pathogenic	0.8659	pathogenic	-2.26	Highly Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
A/I	0.657	likely_pathogenic	0.6634	pathogenic	0.164	Stabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
A/K	0.8921	likely_pathogenic	0.88	pathogenic	-1.206	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
A/L	0.5344	ambiguous	0.511	ambiguous	0.164	Stabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
A/M	0.5025	ambiguous	0.4908	ambiguous	-0.314	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
A/N	0.8218	likely_pathogenic	0.8204	pathogenic	-1.715	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
A/P	0.9929	likely_pathogenic	0.9929	pathogenic	-0.279	Destabilizing	1.0	D	0.809	deleterious	N	0.484766233	None	None	N
A/Q	0.7712	likely_pathogenic	0.7543	pathogenic	-1.385	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
A/R	0.8138	likely_pathogenic	0.7916	pathogenic	-1.465	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
A/S	0.1664	likely_benign	0.1713	benign	-2.081	Highly Destabilizing	1.0	D	0.597	neutral	N	0.394037799	None	None	N
A/T	0.2649	likely_benign	0.2654	benign	-1.685	Destabilizing	1.0	D	0.708	prob.delet.	N	0.451891237	None	None	N
A/V	0.3661	ambiguous	0.3692	ambiguous	-0.279	Destabilizing	1.0	D	0.652	neutral	N	0.449005648	None	None	N
A/W	0.9541	likely_pathogenic	0.9473	pathogenic	-1.477	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
A/Y	0.8382	likely_pathogenic	0.8136	pathogenic	-0.952	Destabilizing	1.0	D	0.808	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.