TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9572	28939;28940;28941	chr2:178709605;178709604;178709603	chr2:179574332;179574331;179574330
N2AB	9255	27988;27989;27990	chr2:178709605;178709604;178709603	chr2:179574332;179574331;179574330
N2A	8328	25207;25208;25209	chr2:178709605;178709604;178709603	chr2:179574332;179574331;179574330
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-81
• Domain position: 80
• Structural Position: 163
• Q(SASA): 0.3837
• 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
A/S	rs2076363568	None	0.919	None	0.579	0.373	0.291694819147	gnomAD-4.0.0	6.84279E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99582E-07	0	0
A/V	None	None	0.919	None	0.641	0.364	0.529561333529	gnomAD-4.0.0	1.59165E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8594E-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
A/C	0.7858	likely_pathogenic	0.774	pathogenic	-0.811	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
A/D	0.8103	likely_pathogenic	0.8835	pathogenic	-0.524	Destabilizing	0.991	D	0.74	deleterious	None	None	None	None	I
A/E	0.7353	likely_pathogenic	0.8348	pathogenic	-0.674	Destabilizing	0.988	D	0.723	prob.delet.	None	None	None	None	I
A/F	0.612	likely_pathogenic	0.6419	pathogenic	-0.933	Destabilizing	0.995	D	0.781	deleterious	None	None	None	None	I
A/G	0.3825	ambiguous	0.4066	ambiguous	-0.207	Destabilizing	0.958	D	0.629	neutral	None	None	None	None	I
A/H	0.8331	likely_pathogenic	0.8792	pathogenic	-0.211	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
A/I	0.5975	likely_pathogenic	0.6184	pathogenic	-0.421	Destabilizing	0.991	D	0.727	prob.delet.	None	None	None	None	I
A/K	0.8615	likely_pathogenic	0.9286	pathogenic	-0.488	Destabilizing	0.991	D	0.726	prob.delet.	None	None	None	None	I
A/L	0.5185	ambiguous	0.5732	pathogenic	-0.421	Destabilizing	0.938	D	0.633	neutral	None	None	None	None	I
A/M	0.5546	ambiguous	0.6056	pathogenic	-0.554	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
A/N	0.7082	likely_pathogenic	0.7884	pathogenic	-0.182	Destabilizing	0.991	D	0.753	deleterious	None	None	None	None	I
A/P	0.9552	likely_pathogenic	0.9648	pathogenic	-0.329	Destabilizing	0.994	D	0.725	prob.delet.	None	None	None	None	I
A/Q	0.7433	likely_pathogenic	0.8323	pathogenic	-0.445	Destabilizing	0.995	D	0.762	deleterious	None	None	None	None	I
A/R	0.7482	likely_pathogenic	0.849	pathogenic	-0.073	Destabilizing	0.991	D	0.744	deleterious	None	None	None	None	I
A/S	0.1856	likely_benign	0.1944	benign	-0.364	Destabilizing	0.919	D	0.579	neutral	None	None	None	None	I
A/T	0.2662	likely_benign	0.3181	benign	-0.445	Destabilizing	0.142	N	0.477	neutral	None	None	None	None	I
A/V	0.2825	likely_benign	0.2979	benign	-0.329	Destabilizing	0.919	D	0.641	neutral	None	None	None	None	I
A/W	0.9535	likely_pathogenic	0.965	pathogenic	-1.024	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
A/Y	0.8215	likely_pathogenic	0.8539	pathogenic	-0.712	Destabilizing	1.0	D	0.784	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.