TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5737	17434;17435;17436	chr2:178731557;178731556;178731555	chr2:179596284;179596283;179596282
N2AB	5420	16483;16484;16485	chr2:178731557;178731556;178731555	chr2:179596284;179596283;179596282
N2A	4493	13702;13703;13704	chr2:178731557;178731556;178731555	chr2:179596284;179596283;179596282
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: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-41
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.634
• 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	rs575592774	0.718	0.985	N	0.375	0.189	0.43656330218	gnomAD-2.1.1	8.18E-06	None	None	None	None	N	None	1.29786E-04	0	None	0	0	None	0	None	0	0	0
E/K	rs575592774	0.718	0.985	N	0.375	0.189	0.43656330218	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	9.66E-05	0	0	0	0	None	0	0	0	2.07641E-04	0
E/K	rs575592774	0.718	0.985	N	0.375	0.189	0.43656330218	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1E-03	None
E/K	rs575592774	0.718	0.985	N	0.375	0.189	0.43656330218	gnomAD-4.0.0	8.08404E-06	None	None	None	None	N	None	6.69057E-05	0	None	0	0	None	1.56745E-05	0	5.09997E-06	1.10468E-05	0
E/Q	rs575592774	0.115	0.983	N	0.397	0.179	0.352476196916	gnomAD-4.0.0	6.86854E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.66412E-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	0.1732	likely_benign	0.1558	benign	-0.274	Destabilizing	0.826	D	0.343	neutral	N	0.494277612	None	None	N
E/C	0.888	likely_pathogenic	0.8655	pathogenic	-0.147	Destabilizing	0.999	D	0.369	neutral	None	None	None	None	N
E/D	0.1193	likely_benign	0.1277	benign	-0.377	Destabilizing	0.015	N	0.124	neutral	N	0.482756722	None	None	N
E/F	0.7974	likely_pathogenic	0.7692	pathogenic	-0.003	Destabilizing	0.991	D	0.392	neutral	None	None	None	None	N
E/G	0.1875	likely_benign	0.1695	benign	-0.487	Destabilizing	0.92	D	0.375	neutral	D	0.52965388	None	None	N
E/H	0.5028	ambiguous	0.4538	ambiguous	0.346	Stabilizing	0.997	D	0.396	neutral	None	None	None	None	N
E/I	0.4313	ambiguous	0.3955	ambiguous	0.254	Stabilizing	0.321	N	0.3	neutral	None	None	None	None	N
E/K	0.1965	likely_benign	0.1512	benign	0.416	Stabilizing	0.985	D	0.375	neutral	N	0.510755901	None	None	N
E/L	0.477	ambiguous	0.4449	ambiguous	0.254	Stabilizing	0.884	D	0.401	neutral	None	None	None	None	N
E/M	0.5682	likely_pathogenic	0.5312	ambiguous	0.19	Stabilizing	0.998	D	0.381	neutral	None	None	None	None	N
E/N	0.267	likely_benign	0.2535	benign	-0.08	Destabilizing	0.939	D	0.377	neutral	None	None	None	None	N
E/P	0.6719	likely_pathogenic	0.5919	pathogenic	0.099	Stabilizing	0.997	D	0.377	neutral	None	None	None	None	N
E/Q	0.1479	likely_benign	0.1324	benign	-0.011	Destabilizing	0.983	D	0.397	neutral	N	0.493346363	None	None	N
E/R	0.3171	likely_benign	0.2511	benign	0.691	Stabilizing	0.991	D	0.379	neutral	None	None	None	None	N
E/S	0.1993	likely_benign	0.1872	benign	-0.204	Destabilizing	0.884	D	0.347	neutral	None	None	None	None	N
E/T	0.2303	likely_benign	0.2103	benign	-0.019	Destabilizing	0.17	N	0.182	neutral	None	None	None	None	N
E/V	0.2551	likely_benign	0.2302	benign	0.099	Stabilizing	0.704	D	0.372	neutral	N	0.513142335	None	None	N
E/W	0.9344	likely_pathogenic	0.9177	pathogenic	0.182	Stabilizing	0.999	D	0.498	neutral	None	None	None	None	N
E/Y	0.6924	likely_pathogenic	0.6469	pathogenic	0.259	Stabilizing	0.997	D	0.396	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.