TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5746	17461;17462;17463	chr2:178731530;178731529;178731528	chr2:179596257;179596256;179596255
N2AB	5429	16510;16511;16512	chr2:178731530;178731529;178731528	chr2:179596257;179596256;179596255
N2A	4502	13729;13730;13731	chr2:178731530;178731529;178731528	chr2:179596257;179596256;179596255
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: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-41
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.4732
• 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/R	rs775732793	0.199	0.863	N	0.397	0.176	0.451213972277	gnomAD-2.1.1	2.87E-05	None	None	None	None	N	None	0	8.52E-05	None	0	0	None	0	None	2.00674E-04	0	0
T/R	rs775732793	0.199	0.863	N	0.397	0.176	0.451213972277	gnomAD-3.1.2	6.57E-05	None	None	None	None	N	None	0	0	0	0	0	None	9.41442E-04	0	0	0	0
T/R	rs775732793	0.199	0.863	N	0.397	0.176	0.451213972277	gnomAD-4.0.0	1.61184E-05	None	None	None	None	N	None	0	5.00634E-05	None	0	0	None	3.28279E-04	0	1.69564E-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	0.0832	likely_benign	0.079	benign	-0.428	Destabilizing	0.27	N	0.285	neutral	N	0.444300756	None	None	N
T/C	0.5015	ambiguous	0.4373	ambiguous	-0.218	Destabilizing	0.995	D	0.357	neutral	None	None	None	None	N
T/D	0.3857	ambiguous	0.305	benign	0.395	Stabilizing	0.007	N	0.205	neutral	None	None	None	None	N
T/E	0.2857	likely_benign	0.2255	benign	0.308	Stabilizing	0.031	N	0.231	neutral	None	None	None	None	N
T/F	0.229	likely_benign	0.1902	benign	-1.043	Destabilizing	0.893	D	0.369	neutral	None	None	None	None	N
T/G	0.2898	likely_benign	0.2552	benign	-0.514	Destabilizing	0.704	D	0.329	neutral	None	None	None	None	N
T/H	0.2477	likely_benign	0.2081	benign	-0.89	Destabilizing	0.981	D	0.339	neutral	None	None	None	None	N
T/I	0.1693	likely_benign	0.1438	benign	-0.323	Destabilizing	0.473	N	0.371	neutral	N	0.455758247	None	None	N
T/K	0.1735	likely_benign	0.1429	benign	-0.179	Destabilizing	0.642	D	0.313	neutral	N	0.488763609	None	None	N
T/L	0.1085	likely_benign	0.0964	benign	-0.323	Destabilizing	0.007	N	0.22	neutral	None	None	None	None	N
T/M	0.0863	likely_benign	0.086	benign	-0.05	Destabilizing	0.893	D	0.363	neutral	None	None	None	None	N
T/N	0.1238	likely_benign	0.1085	benign	0.044	Stabilizing	0.704	D	0.201	neutral	None	None	None	None	N
T/P	0.1366	likely_benign	0.1243	benign	-0.333	Destabilizing	0.006	N	0.217	neutral	N	0.448647783	None	None	N
T/Q	0.2036	likely_benign	0.1743	benign	-0.2	Destabilizing	0.704	D	0.391	neutral	None	None	None	None	N
T/R	0.1399	likely_benign	0.1162	benign	0.008	Stabilizing	0.863	D	0.397	neutral	N	0.447629063	None	None	N
T/S	0.109	likely_benign	0.0987	benign	-0.195	Destabilizing	0.065	N	0.131	neutral	N	0.389444764	None	None	N
T/V	0.1395	likely_benign	0.1192	benign	-0.333	Destabilizing	0.543	D	0.192	neutral	None	None	None	None	N
T/W	0.5563	ambiguous	0.4981	ambiguous	-1.032	Destabilizing	0.995	D	0.419	neutral	None	None	None	None	N
T/Y	0.2654	likely_benign	0.2284	benign	-0.737	Destabilizing	0.981	D	0.358	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.