TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23814	71665;71666;71667	chr2:178574692;178574691;178574690	chr2:179439419;179439418;179439417
N2AB	22173	66742;66743;66744	chr2:178574692;178574691;178574690	chr2:179439419;179439418;179439417
N2A	21246	63961;63962;63963	chr2:178574692;178574691;178574690	chr2:179439419;179439418;179439417
N2B	14749	44470;44471;44472	chr2:178574692;178574691;178574690	chr2:179439419;179439418;179439417
Novex-1	14874	44845;44846;44847	chr2:178574692;178574691;178574690	chr2:179439419;179439418;179439417
Novex-2	14941	45046;45047;45048	chr2:178574692;178574691;178574690	chr2:179439419;179439418;179439417
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-60
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.1666
• 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
T/A	rs1425003858	-0.553	0.085	N	0.537	0.085	0.239901079897	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.59E-05	None	0	None	0	0	0
T/A	rs1425003858	-0.553	0.085	N	0.537	0.085	0.239901079897	gnomAD-4.0.0	1.59227E-06	None	None	None	None	N	None	0	0	None	0	2.77778E-05	None	0	0	0	0	0
T/I	None	None	0.001	N	0.513	0.112	0.293147016451	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	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
T/A	0.0828	likely_benign	0.077	benign	-0.908	Destabilizing	0.085	N	0.537	neutral	N	0.500538907	None	None	N
T/C	0.3202	likely_benign	0.2987	benign	-0.556	Destabilizing	0.98	D	0.671	prob.neutral	None	None	None	None	N
T/D	0.3428	ambiguous	0.3076	benign	0.146	Stabilizing	0.229	N	0.729	deleterious	None	None	None	None	N
T/E	0.2728	likely_benign	0.2529	benign	0.18	Stabilizing	0.372	N	0.728	deleterious	None	None	None	None	N
T/F	0.2255	likely_benign	0.2	benign	-0.862	Destabilizing	0.675	D	0.723	deleterious	None	None	None	None	N
T/G	0.2584	likely_benign	0.2327	benign	-1.193	Destabilizing	0.229	N	0.667	prob.neutral	None	None	None	None	N
T/H	0.2589	likely_benign	0.2451	benign	-1.269	Destabilizing	0.808	D	0.683	prob.neutral	None	None	None	None	N
T/I	0.12	likely_benign	0.1045	benign	-0.232	Destabilizing	0.001	N	0.513	neutral	N	0.512180053	None	None	N
T/K	0.2951	likely_benign	0.2631	benign	-0.586	Destabilizing	0.309	N	0.716	prob.delet.	N	0.491650065	None	None	N
T/L	0.0809	likely_benign	0.0786	benign	-0.232	Destabilizing	0.04	N	0.669	prob.neutral	None	None	None	None	N
T/M	0.0944	likely_benign	0.0911	benign	-0.114	Destabilizing	0.675	D	0.693	prob.delet.	None	None	None	None	N
T/N	0.1087	likely_benign	0.0994	benign	-0.601	Destabilizing	0.001	N	0.342	neutral	None	None	None	None	N
T/P	0.114	likely_benign	0.1215	benign	-0.425	Destabilizing	0.761	D	0.801	deleterious	N	0.474315098	None	None	N
T/Q	0.2369	likely_benign	0.2242	benign	-0.674	Destabilizing	0.808	D	0.784	deleterious	None	None	None	None	N
T/R	0.2812	likely_benign	0.2512	benign	-0.403	Destabilizing	0.61	D	0.801	deleterious	N	0.513910849	None	None	N
T/S	0.0961	likely_benign	0.0889	benign	-0.981	Destabilizing	0.006	N	0.379	neutral	N	0.502114988	None	None	N
T/V	0.0964	likely_benign	0.0878	benign	-0.425	Destabilizing	0.003	N	0.42	neutral	None	None	None	None	N
T/W	0.637	likely_pathogenic	0.6001	pathogenic	-0.778	Destabilizing	0.98	D	0.725	deleterious	None	None	None	None	N
T/Y	0.2557	likely_benign	0.2304	benign	-0.542	Destabilizing	0.808	D	0.713	prob.delet.	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.