TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7259	22000;22001;22002	chr2:178723232;178723231;178723230	chr2:179587959;179587958;179587957
N2AB	6942	21049;21050;21051	chr2:178723232;178723231;178723230	chr2:179587959;179587958;179587957
N2A	6015	18268;18269;18270	chr2:178723232;178723231;178723230	chr2:179587959;179587958;179587957
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-57
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.11
• 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
I/M	rs727505220	-0.964	1.0	N	0.747	0.346	0.602320007227	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
I/M	rs727505220	-0.964	1.0	N	0.747	0.346	0.602320007227	gnomAD-4.0.0	6.84303E-07	None	None	None	None	I	None	0	0	None	0	2.52029E-05	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
I/A	0.7112	likely_pathogenic	0.7261	pathogenic	-2.176	Highly Destabilizing	0.999	D	0.574	neutral	None	None	None	None	I
I/C	0.9035	likely_pathogenic	0.886	pathogenic	-1.601	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	I
I/D	0.9852	likely_pathogenic	0.9822	pathogenic	-1.71	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
I/E	0.9716	likely_pathogenic	0.9683	pathogenic	-1.567	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
I/F	0.4877	ambiguous	0.3649	ambiguous	-1.298	Destabilizing	1.0	D	0.757	deleterious	N	0.50110124	None	None	I
I/G	0.9522	likely_pathogenic	0.9509	pathogenic	-2.648	Highly Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	I
I/H	0.9536	likely_pathogenic	0.94	pathogenic	-1.947	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
I/K	0.9262	likely_pathogenic	0.9207	pathogenic	-1.528	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	I
I/L	0.2383	likely_benign	0.2421	benign	-0.869	Destabilizing	0.993	D	0.444	neutral	N	0.494055652	None	None	I
I/M	0.3181	likely_benign	0.3099	benign	-0.89	Destabilizing	1.0	D	0.747	deleterious	N	0.497480389	None	None	I
I/N	0.8565	likely_pathogenic	0.8448	pathogenic	-1.601	Destabilizing	1.0	D	0.815	deleterious	N	0.506381159	None	None	I
I/P	0.8433	likely_pathogenic	0.8171	pathogenic	-1.279	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	I
I/Q	0.94	likely_pathogenic	0.9316	pathogenic	-1.581	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
I/R	0.8859	likely_pathogenic	0.8745	pathogenic	-1.177	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
I/S	0.8231	likely_pathogenic	0.8205	pathogenic	-2.371	Highly Destabilizing	1.0	D	0.777	deleterious	N	0.483161569	None	None	I
I/T	0.774	likely_pathogenic	0.7856	pathogenic	-2.086	Highly Destabilizing	1.0	D	0.765	deleterious	N	0.487769925	None	None	I
I/V	0.0744	likely_benign	0.0785	benign	-1.279	Destabilizing	0.993	D	0.416	neutral	N	0.507353023	None	None	I
I/W	0.9819	likely_pathogenic	0.9701	pathogenic	-1.498	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
I/Y	0.8986	likely_pathogenic	0.8466	pathogenic	-1.231	Destabilizing	1.0	D	0.792	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.