TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4967	15124;15125;15126	chr2:178735547;178735546;178735545	chr2:179600274;179600273;179600272
N2AB	4650	14173;14174;14175	chr2:178735547;178735546;178735545	chr2:179600274;179600273;179600272
N2A	3723	11392;11393;11394	chr2:178735547;178735546;178735545	chr2:179600274;179600273;179600272
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: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-32
• Domain position: 80
• Structural Position: 164
• Q(SASA): 0.2552
• Predicted PPI site: I

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/A	None	None	1.0	D	0.744	0.713	0.576708290288	gnomAD-4.0.0	1.62461E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.08356E-05
G/R	rs267599070	0.107	1.0	D	0.847	0.738	0.870683688638	gnomAD-2.1.1	4.21E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	9.17E-06	0
G/R	rs267599070	0.107	1.0	D	0.847	0.738	0.870683688638	gnomAD-4.0.0	3.24923E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.79811E-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
G/A	0.4323	ambiguous	0.5169	ambiguous	-0.127	Destabilizing	1.0	D	0.744	deleterious	D	0.774420591	None	None	I
G/C	0.748	likely_pathogenic	0.821	pathogenic	-0.771	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
G/D	0.6965	likely_pathogenic	0.7574	pathogenic	-0.307	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
G/E	0.7451	likely_pathogenic	0.8137	pathogenic	-0.474	Destabilizing	1.0	D	0.823	deleterious	D	0.769205323	None	None	I
G/F	0.9242	likely_pathogenic	0.9437	pathogenic	-0.974	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
G/H	0.8869	likely_pathogenic	0.9226	pathogenic	-0.376	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
G/I	0.8757	likely_pathogenic	0.9097	pathogenic	-0.383	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
G/K	0.8743	likely_pathogenic	0.9084	pathogenic	-0.424	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
G/L	0.8824	likely_pathogenic	0.9185	pathogenic	-0.383	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	I
G/M	0.9124	likely_pathogenic	0.9392	pathogenic	-0.387	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	I
G/N	0.7715	likely_pathogenic	0.8346	pathogenic	-0.145	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
G/P	0.9921	likely_pathogenic	0.9936	pathogenic	-0.27	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
G/Q	0.8054	likely_pathogenic	0.8629	pathogenic	-0.417	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
G/R	0.7433	likely_pathogenic	0.8045	pathogenic	-0.083	Destabilizing	1.0	D	0.847	deleterious	D	0.789021906	None	None	I
G/S	0.3034	likely_benign	0.3728	ambiguous	-0.278	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
G/T	0.6922	likely_pathogenic	0.7463	pathogenic	-0.378	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
G/V	0.7828	likely_pathogenic	0.8383	pathogenic	-0.27	Destabilizing	1.0	D	0.817	deleterious	D	0.842548789	None	None	I
G/W	0.8885	likely_pathogenic	0.9125	pathogenic	-1.103	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
G/Y	0.8853	likely_pathogenic	0.9116	pathogenic	-0.747	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I

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.