TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24787	74584;74585;74586	chr2:178571773;178571772;178571771	chr2:179436500;179436499;179436498
N2AB	23146	69661;69662;69663	chr2:178571773;178571772;178571771	chr2:179436500;179436499;179436498
N2A	22219	66880;66881;66882	chr2:178571773;178571772;178571771	chr2:179436500;179436499;179436498
N2B	15722	47389;47390;47391	chr2:178571773;178571772;178571771	chr2:179436500;179436499;179436498
Novex-1	15847	47764;47765;47766	chr2:178571773;178571772;178571771	chr2:179436500;179436499;179436498
Novex-2	15914	47965;47966;47967	chr2:178571773;178571772;178571771	chr2:179436500;179436499;179436498
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-133
• Domain position: 72
• Structural Position: 155
• Q(SASA): 0.1723
• 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
V/E	None	None	0.055	N	0.539	0.116	0.261217442401	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
V/A	0.0837	likely_benign	0.0792	benign	-2.089	Highly Destabilizing	0.005	N	0.349	neutral	N	0.449743861	None	None	N
V/C	0.4133	ambiguous	0.4093	ambiguous	-1.627	Destabilizing	0.356	N	0.581	neutral	None	None	None	None	N
V/D	0.1965	likely_benign	0.1953	benign	-2.823	Highly Destabilizing	0.072	N	0.609	neutral	None	None	None	None	N
V/E	0.1351	likely_benign	0.1331	benign	-2.616	Highly Destabilizing	0.055	N	0.539	neutral	N	0.40108591	None	None	N
V/F	0.1319	likely_benign	0.1299	benign	-1.216	Destabilizing	0.072	N	0.599	neutral	None	None	None	None	N
V/G	0.1512	likely_benign	0.1452	benign	-2.611	Highly Destabilizing	0.055	N	0.563	neutral	N	0.458248701	None	None	N
V/H	0.2461	likely_benign	0.2457	benign	-2.448	Highly Destabilizing	0.864	D	0.598	neutral	None	None	None	None	N
V/I	0.0658	likely_benign	0.065	benign	-0.629	Destabilizing	None	N	0.197	neutral	None	None	None	None	N
V/K	0.1386	likely_benign	0.1417	benign	-1.746	Destabilizing	0.072	N	0.539	neutral	None	None	None	None	N
V/L	0.1035	likely_benign	0.1035	benign	-0.629	Destabilizing	None	N	0.205	neutral	N	0.47885326	None	None	N
V/M	0.0777	likely_benign	0.0778	benign	-0.675	Destabilizing	0.002	N	0.351	neutral	N	0.456285832	None	None	N
V/N	0.1359	likely_benign	0.1332	benign	-2.054	Highly Destabilizing	0.072	N	0.615	neutral	None	None	None	None	N
V/P	0.7902	likely_pathogenic	0.7724	pathogenic	-1.09	Destabilizing	0.356	N	0.601	neutral	None	None	None	None	N
V/Q	0.1325	likely_benign	0.1323	benign	-1.897	Destabilizing	0.214	N	0.602	neutral	None	None	None	None	N
V/R	0.1204	likely_benign	0.1231	benign	-1.582	Destabilizing	0.214	N	0.619	neutral	None	None	None	None	N
V/S	0.0948	likely_benign	0.0929	benign	-2.63	Highly Destabilizing	0.016	N	0.495	neutral	None	None	None	None	N
V/T	0.0652	likely_benign	0.0644	benign	-2.288	Highly Destabilizing	None	N	0.166	neutral	None	None	None	None	N
V/W	0.5547	ambiguous	0.549	ambiguous	-1.797	Destabilizing	0.864	D	0.614	neutral	None	None	None	None	N
V/Y	0.3025	likely_benign	0.2993	benign	-1.432	Destabilizing	0.356	N	0.593	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.