TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5940	18043;18044;18045	chr2:178730715;178730714;178730713	chr2:179595442;179595441;179595440
N2AB	5623	17092;17093;17094	chr2:178730715;178730714;178730713	chr2:179595442;179595441;179595440
N2A	4696	14311;14312;14313	chr2:178730715;178730714;178730713	chr2:179595442;179595441;179595440
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: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-43
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.0902
• Site annotation: disulfide
• 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
C/R	rs374882815	-1.557	0.879	D	0.875	0.726	None	gnomAD-2.1.1	1.4374E-04	None	None	disulfide	None	N	None	0	0	None	9.71E-05	0	None	0	None	4E-05	2.8477E-04	2.82566E-04
C/R	rs374882815	-1.557	0.879	D	0.875	0.726	None	gnomAD-3.1.2	1.24857E-04	None	None	disulfide	None	N	None	0	6.55E-05	0	0	0	None	1.88395E-04	0	2.35225E-04	0	0
C/R	rs374882815	-1.557	0.879	D	0.875	0.726	None	gnomAD-4.0.0	1.11564E-04	None	None	disulfide	None	N	None	0	1.66778E-05	None	3.37998E-05	0	None	7.81397E-05	1.64582E-04	1.43267E-04	2.1965E-05	1.60149E-05

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
C/A	0.869	likely_pathogenic	0.8412	pathogenic	-1.258	Destabilizing	0.358	N	0.697	prob.neutral	None	None	disulfide	None	N
C/D	0.9986	likely_pathogenic	0.9985	pathogenic	-1.603	Destabilizing	0.967	D	0.875	deleterious	None	None	disulfide	None	N
C/E	0.9995	likely_pathogenic	0.9995	pathogenic	-1.35	Destabilizing	0.906	D	0.871	deleterious	None	None	disulfide	None	N
C/F	0.9593	likely_pathogenic	0.9459	pathogenic	-0.727	Destabilizing	0.642	D	0.848	deleterious	D	0.564218507	disulfide	None	N
C/G	0.6318	likely_pathogenic	0.5653	pathogenic	-1.591	Destabilizing	0.782	D	0.86	deleterious	D	0.534757947	disulfide	None	N
C/H	0.9986	likely_pathogenic	0.9984	pathogenic	-1.773	Destabilizing	0.991	D	0.879	deleterious	None	None	disulfide	None	N
C/I	0.953	likely_pathogenic	0.9416	pathogenic	-0.346	Destabilizing	0.906	D	0.795	deleterious	None	None	disulfide	None	N
C/K	0.9998	likely_pathogenic	0.9997	pathogenic	-0.855	Destabilizing	0.906	D	0.876	deleterious	None	None	disulfide	None	N
C/L	0.9611	likely_pathogenic	0.948	pathogenic	-0.346	Destabilizing	0.404	N	0.765	deleterious	None	None	disulfide	None	N
C/M	0.9697	likely_pathogenic	0.9596	pathogenic	-0.259	Destabilizing	0.991	D	0.785	deleterious	None	None	disulfide	None	N
C/N	0.9914	likely_pathogenic	0.9904	pathogenic	-1.587	Destabilizing	0.967	D	0.878	deleterious	None	None	disulfide	None	N
C/P	0.9996	likely_pathogenic	0.9996	pathogenic	-0.631	Destabilizing	0.967	D	0.875	deleterious	None	None	disulfide	None	N
C/Q	0.999	likely_pathogenic	0.9988	pathogenic	-1.057	Destabilizing	0.967	D	0.887	deleterious	None	None	disulfide	None	N
C/R	0.9981	likely_pathogenic	0.998	pathogenic	-1.39	Destabilizing	0.879	D	0.875	deleterious	D	0.564471997	disulfide	None	N
C/S	0.8979	likely_pathogenic	0.8841	pathogenic	-1.769	Destabilizing	0.879	D	0.815	deleterious	D	0.537720461	disulfide	None	N
C/T	0.9428	likely_pathogenic	0.9306	pathogenic	-1.35	Destabilizing	0.906	D	0.807	deleterious	None	None	disulfide	None	N
C/V	0.8607	likely_pathogenic	0.829	pathogenic	-0.631	Destabilizing	0.733	D	0.801	deleterious	None	None	disulfide	None	N
C/W	0.9972	likely_pathogenic	0.9963	pathogenic	-1.206	Destabilizing	0.007	N	0.693	prob.neutral	D	0.564471997	disulfide	None	N
C/Y	0.9898	likely_pathogenic	0.9882	pathogenic	-0.929	Destabilizing	0.642	D	0.848	deleterious	D	0.552862202	disulfide	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.