TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18431	55516;55517;55518	chr2:178601893;178601892;178601891	chr2:179466620;179466619;179466618
N2AB	16790	50593;50594;50595	chr2:178601893;178601892;178601891	chr2:179466620;179466619;179466618
N2A	15863	47812;47813;47814	chr2:178601893;178601892;178601891	chr2:179466620;179466619;179466618
N2B	9366	28321;28322;28323	chr2:178601893;178601892;178601891	chr2:179466620;179466619;179466618
Novex-1	9491	28696;28697;28698	chr2:178601893;178601892;178601891	chr2:179466620;179466619;179466618
Novex-2	9558	28897;28898;28899	chr2:178601893;178601892;178601891	chr2:179466620;179466619;179466618
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-115
• Domain position: 50
• Structural Position: 70
• Q(SASA): 0.7996
• 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
E/K	rs756341923	0.517	0.986	N	0.473	0.219	0.305410167561	gnomAD-2.1.1	1.22E-05	None	None	None	None	N	None	0	0	None	1.0008E-04	0	None	0	None	0	1.79E-05	0
E/K	rs756341923	0.517	0.986	N	0.473	0.219	0.305410167561	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs756341923	0.517	0.986	N	0.473	0.219	0.305410167561	gnomAD-4.0.0	9.30744E-06	None	None	None	None	N	None	2.67401E-05	0	None	6.77002E-05	0	None	0	0	8.48163E-06	0	1.60369E-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
E/A	0.1025	likely_benign	0.0942	benign	-0.354	Destabilizing	0.961	D	0.497	neutral	N	0.477565181	None	None	N
E/C	0.747	likely_pathogenic	0.6942	pathogenic	0.007	Stabilizing	1.0	D	0.599	neutral	None	None	None	None	N
E/D	0.1085	likely_benign	0.1063	benign	-0.346	Destabilizing	0.91	D	0.431	neutral	N	0.433811617	None	None	N
E/F	0.6835	likely_pathogenic	0.6387	pathogenic	-0.272	Destabilizing	0.999	D	0.532	neutral	None	None	None	None	N
E/G	0.1339	likely_benign	0.1335	benign	-0.563	Destabilizing	0.98	D	0.469	neutral	N	0.429960448	None	None	N
E/H	0.4168	ambiguous	0.3855	ambiguous	-0.133	Destabilizing	0.996	D	0.469	neutral	None	None	None	None	N
E/I	0.2538	likely_benign	0.2077	benign	0.162	Stabilizing	0.999	D	0.535	neutral	None	None	None	None	N
E/K	0.1166	likely_benign	0.1185	benign	0.255	Stabilizing	0.986	D	0.473	neutral	N	0.450186579	None	None	N
E/L	0.2968	likely_benign	0.2526	benign	0.162	Stabilizing	0.996	D	0.465	neutral	None	None	None	None	N
E/M	0.3672	ambiguous	0.3209	benign	0.292	Stabilizing	1.0	D	0.516	neutral	None	None	None	None	N
E/N	0.22	likely_benign	0.2008	benign	0.007	Stabilizing	0.996	D	0.425	neutral	None	None	None	None	N
E/P	0.3615	ambiguous	0.3726	ambiguous	0.01	Stabilizing	0.092	N	0.259	neutral	None	None	None	None	N
E/Q	0.1323	likely_benign	0.1272	benign	0.04	Stabilizing	0.709	D	0.241	neutral	N	0.496767017	None	None	N
E/R	0.2248	likely_benign	0.2258	benign	0.437	Stabilizing	0.97	D	0.431	neutral	None	None	None	None	N
E/S	0.1428	likely_benign	0.134	benign	-0.18	Destabilizing	0.97	D	0.449	neutral	None	None	None	None	N
E/T	0.1611	likely_benign	0.1411	benign	-0.015	Destabilizing	0.985	D	0.469	neutral	None	None	None	None	N
E/V	0.1521	likely_benign	0.1302	benign	0.01	Stabilizing	0.994	D	0.437	neutral	N	0.42015446	None	None	N
E/W	0.8334	likely_pathogenic	0.8247	pathogenic	-0.145	Destabilizing	1.0	D	0.614	neutral	None	None	None	None	N
E/Y	0.5558	ambiguous	0.5154	ambiguous	-0.036	Destabilizing	0.999	D	0.517	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.