TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26017	78274;78275;78276	chr2:178568083;178568082;178568081	chr2:179432810;179432809;179432808
N2AB	24376	73351;73352;73353	chr2:178568083;178568082;178568081	chr2:179432810;179432809;179432808
N2A	23449	70570;70571;70572	chr2:178568083;178568082;178568081	chr2:179432810;179432809;179432808
N2B	16952	51079;51080;51081	chr2:178568083;178568082;178568081	chr2:179432810;179432809;179432808
Novex-1	17077	51454;51455;51456	chr2:178568083;178568082;178568081	chr2:179432810;179432809;179432808
Novex-2	17144	51655;51656;51657	chr2:178568083;178568082;178568081	chr2:179432810;179432809;179432808
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-77
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.4948
• 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
N/D	None	None	0.001	N	0.07	0.103	0.119812018005	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-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
N/A	0.4695	ambiguous	0.4492	ambiguous	-0.624	Destabilizing	0.742	D	0.427	neutral	None	None	None	None	I
N/C	0.5807	likely_pathogenic	0.564	pathogenic	0.145	Stabilizing	0.996	D	0.469	neutral	None	None	None	None	I
N/D	0.0527	likely_benign	0.0522	benign	-0.929	Destabilizing	0.001	N	0.07	neutral	N	0.335717428	None	None	I
N/E	0.7323	likely_pathogenic	0.7302	pathogenic	-0.902	Destabilizing	0.206	N	0.233	neutral	None	None	None	None	I
N/F	0.88	likely_pathogenic	0.8774	pathogenic	-0.838	Destabilizing	0.984	D	0.491	neutral	None	None	None	None	I
N/G	0.4529	ambiguous	0.4397	ambiguous	-0.877	Destabilizing	0.543	D	0.329	neutral	None	None	None	None	I
N/H	0.313	likely_benign	0.3116	benign	-0.944	Destabilizing	0.979	D	0.425	neutral	N	0.509726033	None	None	I
N/I	0.6745	likely_pathogenic	0.6506	pathogenic	-0.02	Destabilizing	0.939	D	0.505	neutral	N	0.510072749	None	None	I
N/K	0.7672	likely_pathogenic	0.7706	pathogenic	-0.11	Destabilizing	0.684	D	0.237	neutral	N	0.471240199	None	None	I
N/L	0.6335	likely_pathogenic	0.6152	pathogenic	-0.02	Destabilizing	0.854	D	0.46	neutral	None	None	None	None	I
N/M	0.736	likely_pathogenic	0.719	pathogenic	0.662	Stabilizing	0.996	D	0.461	neutral	None	None	None	None	I
N/P	0.8296	likely_pathogenic	0.8084	pathogenic	-0.194	Destabilizing	0.854	D	0.446	neutral	None	None	None	None	I
N/Q	0.7253	likely_pathogenic	0.7186	pathogenic	-0.894	Destabilizing	0.854	D	0.356	neutral	None	None	None	None	I
N/R	0.7583	likely_pathogenic	0.7734	pathogenic	-0.011	Destabilizing	0.854	D	0.367	neutral	None	None	None	None	I
N/S	0.103	likely_benign	0.0981	benign	-0.568	Destabilizing	0.472	N	0.354	neutral	N	0.472263723	None	None	I
N/T	0.1675	likely_benign	0.1518	benign	-0.382	Destabilizing	0.684	D	0.241	neutral	N	0.461662727	None	None	I
N/V	0.5978	likely_pathogenic	0.5742	pathogenic	-0.194	Destabilizing	0.953	D	0.454	neutral	None	None	None	None	I
N/W	0.964	likely_pathogenic	0.9654	pathogenic	-0.7	Destabilizing	0.996	D	0.586	neutral	None	None	None	None	I
N/Y	0.5019	ambiguous	0.4961	ambiguous	-0.425	Destabilizing	0.979	D	0.472	neutral	N	0.491207786	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.