TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32961	99106;99107;99108	chr2:178539054;178539053;178539052	chr2:179403781;179403780;179403779
N2AB	31320	94183;94184;94185	chr2:178539054;178539053;178539052	chr2:179403781;179403780;179403779
N2A	30393	91402;91403;91404	chr2:178539054;178539053;178539052	chr2:179403781;179403780;179403779
N2B	23896	71911;71912;71913	chr2:178539054;178539053;178539052	chr2:179403781;179403780;179403779
Novex-1	24021	72286;72287;72288	chr2:178539054;178539053;178539052	chr2:179403781;179403780;179403779
Novex-2	24088	72487;72488;72489	chr2:178539054;178539053;178539052	chr2:179403781;179403780;179403779
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Fn3-128
• Domain position: 66
• Structural Position: 96
• Q(SASA): 0.485
• 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
G/E	rs1225559660	-0.46	1.0	N	0.768	0.508	0.515995215087	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
G/E	rs1225559660	-0.46	1.0	N	0.768	0.508	0.515995215087	gnomAD-4.0.0	3.18268E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86558E-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
G/A	0.4544	ambiguous	0.4724	ambiguous	-0.217	Destabilizing	1.0	D	0.694	prob.neutral	N	0.50164272	None	None	N
G/C	0.7291	likely_pathogenic	0.7411	pathogenic	-0.746	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
G/D	0.7423	likely_pathogenic	0.7709	pathogenic	-0.552	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
G/E	0.8398	likely_pathogenic	0.8597	pathogenic	-0.718	Destabilizing	1.0	D	0.768	deleterious	N	0.472155706	None	None	N
G/F	0.9595	likely_pathogenic	0.9693	pathogenic	-1.001	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
G/H	0.8762	likely_pathogenic	0.9055	pathogenic	-0.511	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
G/I	0.9321	likely_pathogenic	0.9438	pathogenic	-0.358	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
G/K	0.9467	likely_pathogenic	0.9564	pathogenic	-0.723	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
G/L	0.9177	likely_pathogenic	0.9303	pathogenic	-0.358	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
G/M	0.9164	likely_pathogenic	0.93	pathogenic	-0.393	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
G/N	0.6145	likely_pathogenic	0.6478	pathogenic	-0.303	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
G/P	0.9911	likely_pathogenic	0.9927	pathogenic	-0.278	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
G/Q	0.8407	likely_pathogenic	0.8649	pathogenic	-0.599	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
G/R	0.8893	likely_pathogenic	0.9101	pathogenic	-0.289	Destabilizing	1.0	D	0.796	deleterious	N	0.470523092	None	None	N
G/S	0.2645	likely_benign	0.2924	benign	-0.435	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
G/T	0.6659	likely_pathogenic	0.6959	pathogenic	-0.532	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
G/V	0.8611	likely_pathogenic	0.8814	pathogenic	-0.278	Destabilizing	1.0	D	0.771	deleterious	D	0.529154724	None	None	N
G/W	0.9316	likely_pathogenic	0.9464	pathogenic	-1.165	Destabilizing	1.0	D	0.742	deleterious	D	0.529408214	None	None	N
G/Y	0.9263	likely_pathogenic	0.9417	pathogenic	-0.799	Destabilizing	1.0	D	0.763	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.