TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14562	43909;43910;43911	chr2:178632210;178632209;178632208	chr2:179496937;179496936;179496935
N2AB	12921	38986;38987;38988	chr2:178632210;178632209;178632208	chr2:179496937;179496936;179496935
N2A	11994	36205;36206;36207	chr2:178632210;178632209;178632208	chr2:179496937;179496936;179496935
N2B	5497	16714;16715;16716	chr2:178632210;178632209;178632208	chr2:179496937;179496936;179496935
Novex-1	5622	17089;17090;17091	chr2:178632210;178632209;178632208	chr2:179496937;179496936;179496935
Novex-2	5689	17290;17291;17292	chr2:178632210;178632209;178632208	chr2:179496937;179496936;179496935
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-96
• Domain position: 66
• Structural Position: 149
• Q(SASA): 0.2041
• 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
D/V	None	None	1.0	D	0.828	0.862	0.72858195137	gnomAD-4.0.0	1.60496E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.45412E-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
D/A	0.5902	likely_pathogenic	0.5871	pathogenic	-0.429	Destabilizing	1.0	D	0.832	deleterious	D	0.720169961	None	None	N
D/C	0.9188	likely_pathogenic	0.927	pathogenic	-0.089	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
D/E	0.6728	likely_pathogenic	0.6343	pathogenic	-0.645	Destabilizing	1.0	D	0.589	neutral	D	0.662512786	None	None	N
D/F	0.9206	likely_pathogenic	0.9024	pathogenic	0.114	Stabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
D/G	0.5982	likely_pathogenic	0.6112	pathogenic	-0.818	Destabilizing	1.0	D	0.783	deleterious	D	0.719432198	None	None	N
D/H	0.6907	likely_pathogenic	0.6998	pathogenic	-0.172	Destabilizing	1.0	D	0.813	deleterious	D	0.71951575	None	None	N
D/I	0.9057	likely_pathogenic	0.8927	pathogenic	0.61	Stabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
D/K	0.8501	likely_pathogenic	0.8713	pathogenic	0.002	Stabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
D/L	0.9006	likely_pathogenic	0.8948	pathogenic	0.61	Stabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
D/M	0.9425	likely_pathogenic	0.9313	pathogenic	1.069	Stabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
D/N	0.2793	likely_benign	0.2673	benign	-0.715	Destabilizing	1.0	D	0.785	deleterious	D	0.684748822	None	None	N
D/P	0.988	likely_pathogenic	0.9907	pathogenic	0.29	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
D/Q	0.8342	likely_pathogenic	0.8279	pathogenic	-0.5	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
D/R	0.876	likely_pathogenic	0.9008	pathogenic	0.097	Stabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
D/S	0.3992	ambiguous	0.3918	ambiguous	-0.94	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
D/T	0.7582	likely_pathogenic	0.7499	pathogenic	-0.587	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
D/V	0.7639	likely_pathogenic	0.7496	pathogenic	0.29	Stabilizing	1.0	D	0.828	deleterious	D	0.719439357	None	None	N
D/W	0.9866	likely_pathogenic	0.9856	pathogenic	0.346	Stabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
D/Y	0.5729	likely_pathogenic	0.5672	pathogenic	0.405	Stabilizing	1.0	D	0.846	deleterious	D	0.71951575	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.