TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20133	60622;60623;60624	chr2:178591328;178591327;178591326	chr2:179456055;179456054;179456053
N2AB	18492	55699;55700;55701	chr2:178591328;178591327;178591326	chr2:179456055;179456054;179456053
N2A	17565	52918;52919;52920	chr2:178591328;178591327;178591326	chr2:179456055;179456054;179456053
N2B	11068	33427;33428;33429	chr2:178591328;178591327;178591326	chr2:179456055;179456054;179456053
Novex-1	11193	33802;33803;33804	chr2:178591328;178591327;178591326	chr2:179456055;179456054;179456053
Novex-2	11260	34003;34004;34005	chr2:178591328;178591327;178591326	chr2:179456055;179456054;179456053
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-120
• Domain position: 54
• Structural Position: 135
• Q(SASA): 0.1495
• 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
S/P	rs769272954	-0.508	0.999	N	0.768	0.508	None	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	1.29232E-04	0	None	0	0	None	0	None	0	0	0
S/P	rs769272954	-0.508	0.999	N	0.768	0.508	None	gnomAD-4.0.0	1.59223E-06	None	None	None	None	N	None	5.66508E-05	0	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
S/A	0.1533	likely_benign	0.1657	benign	-0.656	Destabilizing	0.973	D	0.502	neutral	N	0.483490737	None	None	N
S/C	0.1697	likely_benign	0.1841	benign	-0.471	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
S/D	0.8512	likely_pathogenic	0.8665	pathogenic	-0.306	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
S/E	0.8249	likely_pathogenic	0.8596	pathogenic	-0.336	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	N
S/F	0.3794	ambiguous	0.4243	ambiguous	-0.966	Destabilizing	0.998	D	0.754	deleterious	None	None	None	None	N
S/G	0.2467	likely_benign	0.2631	benign	-0.868	Destabilizing	0.996	D	0.552	neutral	None	None	None	None	N
S/H	0.4966	ambiguous	0.5445	ambiguous	-1.437	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
S/I	0.3978	ambiguous	0.4564	ambiguous	-0.207	Destabilizing	0.995	D	0.719	prob.delet.	None	None	None	None	N
S/K	0.8867	likely_pathogenic	0.9201	pathogenic	-0.693	Destabilizing	0.996	D	0.653	neutral	None	None	None	None	N
S/L	0.1728	likely_benign	0.2027	benign	-0.207	Destabilizing	0.978	D	0.627	neutral	D	0.529576522	None	None	N
S/M	0.3538	ambiguous	0.4006	ambiguous	0.151	Stabilizing	0.96	D	0.545	neutral	None	None	None	None	N
S/N	0.3762	ambiguous	0.4316	ambiguous	-0.598	Destabilizing	0.999	D	0.656	neutral	None	None	None	None	N
S/P	0.958	likely_pathogenic	0.9543	pathogenic	-0.325	Destabilizing	0.999	D	0.768	deleterious	N	0.504521508	None	None	N
S/Q	0.6613	likely_pathogenic	0.7145	pathogenic	-0.825	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
S/R	0.7847	likely_pathogenic	0.8287	pathogenic	-0.557	Destabilizing	0.999	D	0.766	deleterious	None	None	None	None	N
S/T	0.1368	likely_benign	0.1532	benign	-0.635	Destabilizing	0.994	D	0.536	neutral	N	0.508969176	None	None	N
S/V	0.3643	ambiguous	0.42	ambiguous	-0.325	Destabilizing	0.983	D	0.697	prob.neutral	None	None	None	None	N
S/W	0.5947	likely_pathogenic	0.6122	pathogenic	-0.934	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
S/Y	0.3324	likely_benign	0.3589	ambiguous	-0.669	Destabilizing	1.0	D	0.757	deleterious	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.