TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1862	5809;5810;5811	chr2:178776280;178776279;178776278	chr2:179641007;179641006;179641005
N2AB	1862	5809;5810;5811	chr2:178776280;178776279;178776278	chr2:179641007;179641006;179641005
N2A	1862	5809;5810;5811	chr2:178776280;178776279;178776278	chr2:179641007;179641006;179641005
N2B	1816	5671;5672;5673	chr2:178776280;178776279;178776278	chr2:179641007;179641006;179641005
Novex-1	1816	5671;5672;5673	chr2:178776280;178776279;178776278	chr2:179641007;179641006;179641005
Novex-2	1816	5671;5672;5673	chr2:178776280;178776279;178776278	chr2:179641007;179641006;179641005
Novex-3	1862	5809;5810;5811	chr2:178776280;178776279;178776278	chr2:179641007;179641006;179641005

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-9
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.1321
• 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/G	rs2092215973	None	0.968	D	0.843	0.496	0.823553591755	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	1.01626E-03	None	0	0	None	0	0	0	0	0
C/S	None	None	0.811	D	0.765	0.388	0.645225581225	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
C/A	0.8718	likely_pathogenic	0.8754	pathogenic	-0.876	Destabilizing	0.702	D	0.725	prob.delet.	None	None	None	None	N
C/D	0.9997	likely_pathogenic	0.9997	pathogenic	-1.719	Destabilizing	0.976	D	0.85	deleterious	None	None	None	None	N
C/E	0.9998	likely_pathogenic	0.9998	pathogenic	-1.46	Destabilizing	0.976	D	0.855	deleterious	None	None	None	None	N
C/F	0.9345	likely_pathogenic	0.9335	pathogenic	-0.417	Destabilizing	0.984	D	0.819	deleterious	D	0.623757801	None	None	N
C/G	0.8591	likely_pathogenic	0.8611	pathogenic	-1.204	Destabilizing	0.968	D	0.843	deleterious	D	0.59252674	None	None	N
C/H	0.9989	likely_pathogenic	0.9989	pathogenic	-1.458	Destabilizing	0.999	D	0.862	deleterious	None	None	None	None	N
C/I	0.8961	likely_pathogenic	0.8806	pathogenic	0.023	Stabilizing	0.976	D	0.803	deleterious	None	None	None	None	N
C/K	0.9999	likely_pathogenic	0.9999	pathogenic	-0.668	Destabilizing	0.976	D	0.852	deleterious	None	None	None	None	N
C/L	0.8891	likely_pathogenic	0.8798	pathogenic	0.023	Stabilizing	0.851	D	0.755	deleterious	None	None	None	None	N
C/M	0.9594	likely_pathogenic	0.9577	pathogenic	-0.1	Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
C/N	0.9973	likely_pathogenic	0.9974	pathogenic	-1.557	Destabilizing	0.976	D	0.855	deleterious	None	None	None	None	N
C/P	0.9997	likely_pathogenic	0.9997	pathogenic	-0.258	Destabilizing	0.988	D	0.854	deleterious	None	None	None	None	N
C/Q	0.9994	likely_pathogenic	0.9993	pathogenic	-0.995	Destabilizing	0.988	D	0.855	deleterious	None	None	None	None	N
C/R	0.9991	likely_pathogenic	0.9991	pathogenic	-1.299	Destabilizing	0.968	D	0.851	deleterious	D	0.738414964	None	None	N
C/S	0.923	likely_pathogenic	0.9261	pathogenic	-1.651	Destabilizing	0.811	D	0.765	deleterious	D	0.701363963	None	None	N
C/T	0.9337	likely_pathogenic	0.9324	pathogenic	-1.23	Destabilizing	0.132	N	0.614	neutral	None	None	None	None	N
C/V	0.7418	likely_pathogenic	0.7194	pathogenic	-0.258	Destabilizing	0.851	D	0.765	deleterious	None	None	None	None	N
C/W	0.997	likely_pathogenic	0.9971	pathogenic	-0.961	Destabilizing	0.999	D	0.837	deleterious	D	0.738414964	None	None	N
C/Y	0.9902	likely_pathogenic	0.9902	pathogenic	-0.65	Destabilizing	0.995	D	0.817	deleterious	D	0.73751645	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.