TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3858	11797;11798;11799	chr2:178741661;178741660;178741659	chr2:179606388;179606387;179606386
N2AB	3541	10846;10847;10848	chr2:178741661;178741660;178741659	chr2:179606388;179606387;179606386
N2A	None	None	chr2:None	chr2:None
N2B	3495	10708;10709;10710	chr2:178741661;178741660;178741659	chr2:179606388;179606387;179606386
Novex-1	3620	11083;11084;11085	chr2:178741661;178741660;178741659	chr2:179606388;179606387;179606386
Novex-2	3687	11284;11285;11286	chr2:178741661;178741660;178741659	chr2:179606388;179606387;179606386
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-27
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.3427
• 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
V/A	rs1242111129	-0.723	None	N	0.113	0.12	None	gnomAD-4.0.0	3.18242E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43271E-05	3.02407E-05

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	0.1125	likely_benign	0.1314	benign	-0.811	Destabilizing	None	N	0.113	neutral	N	0.472620702	None	None	I
V/C	0.5181	ambiguous	0.5306	ambiguous	-0.714	Destabilizing	0.245	N	0.333	neutral	None	None	None	None	I
V/D	0.1386	likely_benign	0.1504	benign	-0.127	Destabilizing	0.009	N	0.39	neutral	None	None	None	None	I
V/E	0.1239	likely_benign	0.1394	benign	-0.129	Destabilizing	None	N	0.148	neutral	N	0.46942826	None	None	I
V/F	0.0845	likely_benign	0.0857	benign	-0.562	Destabilizing	0.044	N	0.411	neutral	None	None	None	None	I
V/G	0.1372	likely_benign	0.148	benign	-1.064	Destabilizing	0.007	N	0.358	neutral	N	0.494455958	None	None	I
V/H	0.2823	likely_benign	0.3031	benign	-0.347	Destabilizing	None	N	0.305	neutral	None	None	None	None	I
V/I	0.0678	likely_benign	0.0717	benign	-0.239	Destabilizing	None	N	0.16	neutral	None	None	None	None	I
V/K	0.1362	likely_benign	0.153	benign	-0.556	Destabilizing	None	N	0.152	neutral	None	None	None	None	I
V/L	0.1184	likely_benign	0.1356	benign	-0.239	Destabilizing	0.001	N	0.239	neutral	N	0.483955649	None	None	I
V/M	0.0805	likely_benign	0.0913	benign	-0.425	Destabilizing	None	N	0.159	neutral	N	0.502341142	None	None	I
V/N	0.1076	likely_benign	0.1227	benign	-0.539	Destabilizing	0.044	N	0.459	neutral	None	None	None	None	I
V/P	0.7392	likely_pathogenic	0.7345	pathogenic	-0.395	Destabilizing	0.044	N	0.46	neutral	None	None	None	None	I
V/Q	0.1474	likely_benign	0.1602	benign	-0.611	Destabilizing	0.022	N	0.421	neutral	None	None	None	None	I
V/R	0.1263	likely_benign	0.1356	benign	-0.143	Destabilizing	None	N	0.288	neutral	None	None	None	None	I
V/S	0.1093	likely_benign	0.126	benign	-1.061	Destabilizing	0.009	N	0.315	neutral	None	None	None	None	I
V/T	0.1168	likely_benign	0.1428	benign	-0.94	Destabilizing	None	N	0.142	neutral	None	None	None	None	I
V/W	0.5838	likely_pathogenic	0.5901	pathogenic	-0.71	Destabilizing	0.788	D	0.396	neutral	None	None	None	None	I
V/Y	0.2724	likely_benign	0.281	benign	-0.395	Destabilizing	0.044	N	0.411	neutral	None	None	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.