TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3838	11737;11738;11739	chr2:178741721;178741720;178741719	chr2:179606448;179606447;179606446
N2AB	3521	10786;10787;10788	chr2:178741721;178741720;178741719	chr2:179606448;179606447;179606446
N2A	None	None	chr2:None	chr2:None
N2B	3475	10648;10649;10650	chr2:178741721;178741720;178741719	chr2:179606448;179606447;179606446
Novex-1	3600	11023;11024;11025	chr2:178741721;178741720;178741719	chr2:179606448;179606447;179606446
Novex-2	3667	11224;11225;11226	chr2:178741721;178741720;178741719	chr2:179606448;179606447;179606446
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-27
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.5681
• 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	0.065	N	0.513	0.076	None	gnomAD-4.0.0	1.36853E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79901E-06	0	0
T/K	rs752583542	-0.114	None	N	0.209	0.096	None	gnomAD-4.0.0	1.36854E-06	None	None	None	None	N	None	2.98793E-05	0	None	0	0	None	0	0	0	0	1.65706E-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
T/A	0.0939	likely_benign	0.0859	benign	-0.359	Destabilizing	0.001	N	0.332	neutral	N	0.459730006	None	None	N
T/C	0.4571	ambiguous	0.4193	ambiguous	-0.336	Destabilizing	0.497	N	0.454	neutral	None	None	None	None	N
T/D	0.5376	ambiguous	0.53	ambiguous	0.581	Stabilizing	0.004	N	0.339	neutral	None	None	None	None	N
T/E	0.3095	likely_benign	0.2828	benign	0.543	Stabilizing	0.002	N	0.325	neutral	None	None	None	None	N
T/F	0.2838	likely_benign	0.2621	benign	-0.748	Destabilizing	0.497	N	0.569	neutral	None	None	None	None	N
T/G	0.3738	ambiguous	0.3494	ambiguous	-0.53	Destabilizing	0.004	N	0.382	neutral	None	None	None	None	N
T/H	0.2213	likely_benign	0.2038	benign	-0.773	Destabilizing	0.138	N	0.577	neutral	None	None	None	None	N
T/I	0.145	likely_benign	0.1283	benign	-0.022	Destabilizing	0.065	N	0.513	neutral	N	0.457193092	None	None	N
T/K	0.0969	likely_benign	0.0908	benign	-0.192	Destabilizing	None	N	0.209	neutral	N	0.446105517	None	None	N
T/L	0.1039	likely_benign	0.0952	benign	-0.022	Destabilizing	0.008	N	0.326	neutral	None	None	None	None	N
T/M	0.0956	likely_benign	0.0887	benign	-0.025	Destabilizing	0.245	N	0.491	neutral	None	None	None	None	N
T/N	0.1627	likely_benign	0.1521	benign	-0.116	Destabilizing	None	N	0.209	neutral	None	None	None	None	N
T/P	0.2437	likely_benign	0.246	benign	-0.103	Destabilizing	0.028	N	0.464	neutral	D	0.585228161	None	None	N
T/Q	0.1795	likely_benign	0.1595	benign	-0.242	Destabilizing	None	N	0.257	neutral	None	None	None	None	N
T/R	0.094	likely_benign	0.0826	benign	-0.032	Destabilizing	None	N	0.215	neutral	N	0.420252172	None	None	N
T/S	0.1493	likely_benign	0.1408	benign	-0.398	Destabilizing	0.003	N	0.341	neutral	N	0.458532783	None	None	N
T/V	0.136	likely_benign	0.12	benign	-0.103	Destabilizing	0.018	N	0.356	neutral	None	None	None	None	N
T/W	0.6307	likely_pathogenic	0.6145	pathogenic	-0.751	Destabilizing	0.788	D	0.509	neutral	None	None	None	None	N
T/Y	0.2778	likely_benign	0.2659	benign	-0.443	Destabilizing	0.085	N	0.541	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.