TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7529	22810;22811;22812	chr2:178722078;178722077;178722076	chr2:179586805;179586804;179586803
N2AB	7212	21859;21860;21861	chr2:178722078;178722077;178722076	chr2:179586805;179586804;179586803
N2A	6285	19078;19079;19080	chr2:178722078;178722077;178722076	chr2:179586805;179586804;179586803
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-60
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.3511
• 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/V	rs1194135723	None	1.0	D	0.813	0.615	0.858599854351	gnomAD-4.0.0	1.59981E-06	None	None	None	None	N	None	5.68117E-05	0	None	0	0	None	0	0	0	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	0.401	ambiguous	0.4442	ambiguous	-0.3	Destabilizing	0.999	D	0.77	deleterious	D	0.61848618	None	None	N
G/C	0.7711	likely_pathogenic	0.7455	pathogenic	-0.941	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
G/D	0.5636	ambiguous	0.5303	ambiguous	-0.458	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
G/E	0.6027	likely_pathogenic	0.5916	pathogenic	-0.619	Destabilizing	1.0	D	0.83	deleterious	D	0.602911506	None	None	N
G/F	0.908	likely_pathogenic	0.9097	pathogenic	-0.966	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
G/H	0.8101	likely_pathogenic	0.796	pathogenic	-0.476	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
G/I	0.8964	likely_pathogenic	0.911	pathogenic	-0.443	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
G/K	0.8343	likely_pathogenic	0.8356	pathogenic	-0.804	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
G/L	0.8068	likely_pathogenic	0.8289	pathogenic	-0.443	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
G/M	0.8411	likely_pathogenic	0.8503	pathogenic	-0.529	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
G/N	0.495	ambiguous	0.4718	ambiguous	-0.487	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
G/P	0.9848	likely_pathogenic	0.9903	pathogenic	-0.363	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
G/Q	0.6761	likely_pathogenic	0.6759	pathogenic	-0.766	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
G/R	0.6956	likely_pathogenic	0.7065	pathogenic	-0.364	Destabilizing	1.0	D	0.859	deleterious	D	0.62797457	None	None	N
G/S	0.1811	likely_benign	0.1994	benign	-0.655	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
G/T	0.4929	ambiguous	0.5436	ambiguous	-0.744	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
G/V	0.7799	likely_pathogenic	0.8127	pathogenic	-0.363	Destabilizing	1.0	D	0.813	deleterious	D	0.628176375	None	None	N
G/W	0.8111	likely_pathogenic	0.8046	pathogenic	-1.103	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
G/Y	0.8579	likely_pathogenic	0.8518	pathogenic	-0.763	Destabilizing	1.0	D	0.829	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.