TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30179	90760;90761;90762	chr2:178552365;178552364;178552363	chr2:179417092;179417091;179417090
N2AB	28538	85837;85838;85839	chr2:178552365;178552364;178552363	chr2:179417092;179417091;179417090
N2A	27611	83056;83057;83058	chr2:178552365;178552364;178552363	chr2:179417092;179417091;179417090
N2B	21114	63565;63566;63567	chr2:178552365;178552364;178552363	chr2:179417092;179417091;179417090
Novex-1	21239	63940;63941;63942	chr2:178552365;178552364;178552363	chr2:179417092;179417091;179417090
Novex-2	21306	64141;64142;64143	chr2:178552365;178552364;178552363	chr2:179417092;179417091;179417090
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGC
• RefSeq wild type template codon: GCG
• Domain: Ig-148
• Domain position: 48
• Structural Position: 122
• Q(SASA): 0.6835
• 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
R/C	rs769360937	-0.573	1.0	N	0.745	0.428	0.731906779097	gnomAD-2.1.1	3.77E-05	None	None	None	None	N	None	4.16E-05	2.97E-05	None	0	5.21E-05	None	1.91791E-04	None	0	1.63E-05	0
R/C	rs769360937	-0.573	1.0	N	0.745	0.428	0.731906779097	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	7.24E-05	0	0	0	1.9305E-04	None	0	0	1.47E-05	0	0
R/C	rs769360937	-0.573	1.0	N	0.745	0.428	0.731906779097	gnomAD-4.0.0	3.26224E-05	None	None	None	None	N	None	6.72676E-05	1.71562E-05	None	0	2.24406E-05	None	0	0	1.11161E-05	3.4391E-04	3.24971E-05
R/G	rs769360937	-0.955	1.0	N	0.593	0.376	0.672020861447	gnomAD-2.1.1	4.28E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.33E-06	0
R/G	rs769360937	-0.955	1.0	N	0.593	0.376	0.672020861447	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
R/G	rs769360937	-0.955	1.0	N	0.593	0.376	0.672020861447	gnomAD-4.0.0	2.3212E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.07831E-05	0	1.62485E-05
R/H	rs149567378	-1.163	1.0	N	0.753	0.403	None	gnomAD-2.1.1	3.2551E-03	None	None	None	None	N	None	2.08247E-04	9.01605E-04	None	1.15128E-03	1.04515E-04	None	2.2189E-02	None	4.2E-05	1.83667E-03	2.98954E-03
R/H	rs149567378	-1.163	1.0	N	0.753	0.403	None	gnomAD-3.1.2	1.8407E-03	None	None	None	None	N	None	2.41348E-04	1.83582E-03	0	8.64055E-04	1.9305E-04	None	0	0	1.74933E-03	2.38391E-02	1.91388E-03
R/H	rs149567378	-1.163	1.0	N	0.753	0.403	None	1000 genomes	6.1901E-03	None	None	None	None	N	None	0	1.4E-03	None	None	0	2E-03	None	None	None	2.86E-02	None
R/H	rs149567378	-1.163	1.0	N	0.753	0.403	None	gnomAD-4.0.0	2.16914E-03	None	None	None	None	N	None	3.09131E-04	1.08508E-03	None	8.47218E-04	2.01975E-04	None	4.74533E-05	4.19463E-03	1.09666E-03	2.12205E-02	2.97542E-03
R/P	rs149567378	-0.334	1.0	D	0.703	0.488	0.593515057505	gnomAD-2.1.1	4.32E-06	None	None	None	None	N	None	0	3.08E-05	None	0	0	None	0	None	0	0	0
R/P	rs149567378	-0.334	1.0	D	0.703	0.488	0.593515057505	gnomAD-4.0.0	1.38834E-06	None	None	None	None	N	None	3.04451E-05	2.3371E-05	None	0	0	None	0	0	0	0	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
R/A	0.7266	likely_pathogenic	0.5677	pathogenic	-0.878	Destabilizing	0.999	D	0.605	neutral	None	None	None	None	N
R/C	0.2666	likely_benign	0.1933	benign	-0.838	Destabilizing	1.0	D	0.745	deleterious	N	0.485367296	None	None	N
R/D	0.8778	likely_pathogenic	0.7704	pathogenic	0.109	Stabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
R/E	0.7205	likely_pathogenic	0.5549	ambiguous	0.201	Stabilizing	0.999	D	0.647	neutral	None	None	None	None	N
R/F	0.77	likely_pathogenic	0.6422	pathogenic	-0.962	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
R/G	0.5846	likely_pathogenic	0.4136	ambiguous	-1.127	Destabilizing	1.0	D	0.593	neutral	N	0.513569706	None	None	N
R/H	0.1482	likely_benign	0.107	benign	-1.375	Destabilizing	1.0	D	0.753	deleterious	N	0.506566376	None	None	N
R/I	0.5054	ambiguous	0.3673	ambiguous	-0.225	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
R/K	0.1885	likely_benign	0.1387	benign	-0.697	Destabilizing	0.998	D	0.511	neutral	None	None	None	None	N
R/L	0.4824	ambiguous	0.3713	ambiguous	-0.225	Destabilizing	1.0	D	0.593	neutral	N	0.503718072	None	None	N
R/M	0.5636	ambiguous	0.4211	ambiguous	-0.44	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
R/N	0.7525	likely_pathogenic	0.622	pathogenic	-0.131	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
R/P	0.9489	likely_pathogenic	0.9191	pathogenic	-0.423	Destabilizing	1.0	D	0.703	prob.neutral	D	0.532328825	None	None	N
R/Q	0.201	likely_benign	0.1459	benign	-0.405	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
R/S	0.7168	likely_pathogenic	0.5699	pathogenic	-0.987	Destabilizing	1.0	D	0.67	neutral	N	0.446112563	None	None	N
R/T	0.5083	ambiguous	0.3518	ambiguous	-0.731	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
R/V	0.5971	likely_pathogenic	0.4552	ambiguous	-0.423	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
R/W	0.3592	ambiguous	0.2676	benign	-0.651	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
R/Y	0.5656	likely_pathogenic	0.4453	ambiguous	-0.33	Destabilizing	1.0	D	0.718	prob.delet.	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.