TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7284	22075;22076;22077	chr2:178723157;178723156;178723155	chr2:179587884;179587883;179587882
N2AB	6967	21124;21125;21126	chr2:178723157;178723156;178723155	chr2:179587884;179587883;179587882
N2A	6040	18343;18344;18345	chr2:178723157;178723156;178723155	chr2:179587884;179587883;179587882
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-57
• Domain position: 55
• Structural Position: 135
• Q(SASA): 0.2361
• 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/I	None	None	0.096	N	0.491	0.326	0.464698922459	gnomAD-4.0.0	5.47474E-06	None	None	None	None	N	None	0	0	None	0	0	None	5.6224E-05	0	4.49788E-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
T/A	0.0968	likely_benign	0.106	benign	-0.986	Destabilizing	0.019	N	0.317	neutral	N	0.520340963	None	None	N
T/C	0.5368	ambiguous	0.5641	pathogenic	-0.699	Destabilizing	0.667	D	0.54	neutral	None	None	None	None	N
T/D	0.5003	ambiguous	0.546	ambiguous	-0.932	Destabilizing	0.22	N	0.475	neutral	None	None	None	None	N
T/E	0.455	ambiguous	0.5134	ambiguous	-0.867	Destabilizing	0.055	N	0.451	neutral	None	None	None	None	N
T/F	0.2734	likely_benign	0.3317	benign	-0.914	Destabilizing	0.497	N	0.561	neutral	None	None	None	None	N
T/G	0.2834	likely_benign	0.3097	benign	-1.301	Destabilizing	0.055	N	0.475	neutral	None	None	None	None	N
T/H	0.298	likely_benign	0.3366	benign	-1.595	Destabilizing	0.667	D	0.559	neutral	None	None	None	None	N
T/I	0.2745	likely_benign	0.3194	benign	-0.214	Destabilizing	0.096	N	0.491	neutral	N	0.508238457	None	None	N
T/K	0.3236	likely_benign	0.3703	ambiguous	-0.803	Destabilizing	None	N	0.227	neutral	None	None	None	None	N
T/L	0.1575	likely_benign	0.1791	benign	-0.214	Destabilizing	None	N	0.23	neutral	None	None	None	None	N
T/M	0.1114	likely_benign	0.1237	benign	0.065	Stabilizing	0.497	N	0.557	neutral	None	None	None	None	N
T/N	0.1247	likely_benign	0.1432	benign	-1.006	Destabilizing	0.096	N	0.392	neutral	D	0.527170935	None	None	N
T/P	0.6731	likely_pathogenic	0.7062	pathogenic	-0.439	Destabilizing	0.301	N	0.539	neutral	N	0.505179844	None	None	N
T/Q	0.3161	likely_benign	0.3457	ambiguous	-1.1	Destabilizing	0.22	N	0.541	neutral	None	None	None	None	N
T/R	0.2467	likely_benign	0.2842	benign	-0.678	Destabilizing	0.124	N	0.485	neutral	None	None	None	None	N
T/S	0.0883	likely_benign	0.1002	benign	-1.236	Destabilizing	None	N	0.171	neutral	N	0.408132965	None	None	N
T/V	0.2278	likely_benign	0.2549	benign	-0.439	Destabilizing	0.055	N	0.374	neutral	None	None	None	None	N
T/W	0.6609	likely_pathogenic	0.7123	pathogenic	-0.91	Destabilizing	0.958	D	0.561	neutral	None	None	None	None	N
T/Y	0.2489	likely_benign	0.2836	benign	-0.63	Destabilizing	0.667	D	0.554	neutral	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.