TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32026	96301;96302;96303	chr2:178544068;178544067;178544066	chr2:179408795;179408794;179408793
N2AB	30385	91378;91379;91380	chr2:178544068;178544067;178544066	chr2:179408795;179408794;179408793
N2A	29458	88597;88598;88599	chr2:178544068;178544067;178544066	chr2:179408795;179408794;179408793
N2B	22961	69106;69107;69108	chr2:178544068;178544067;178544066	chr2:179408795;179408794;179408793
Novex-1	23086	69481;69482;69483	chr2:178544068;178544067;178544066	chr2:179408795;179408794;179408793
Novex-2	23153	69682;69683;69684	chr2:178544068;178544067;178544066	chr2:179408795;179408794;179408793
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-153
• Domain position: 10
• Structural Position: 16
• Q(SASA): 0.1332
• 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
I/L	None	None	None	N	0.112	0.214	0.0954503805726	gnomAD-4.0.0	1.59198E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43324E-05	0
I/T	rs998031380	None	0.012	N	0.441	0.333	0.677706433072	gnomAD-4.0.0	1.3687E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79925E-06	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
I/A	0.5452	ambiguous	0.5533	ambiguous	-1.993	Destabilizing	0.016	N	0.382	neutral	None	None	None	None	N
I/C	0.7179	likely_pathogenic	0.7133	pathogenic	-1.257	Destabilizing	0.356	N	0.537	neutral	None	None	None	None	N
I/D	0.9742	likely_pathogenic	0.9711	pathogenic	-1.512	Destabilizing	0.356	N	0.594	neutral	None	None	None	None	N
I/E	0.9265	likely_pathogenic	0.9147	pathogenic	-1.357	Destabilizing	0.356	N	0.607	neutral	None	None	None	None	N
I/F	0.3821	ambiguous	0.3799	ambiguous	-1.078	Destabilizing	0.029	N	0.509	neutral	D	0.534369053	None	None	N
I/G	0.8717	likely_pathogenic	0.8789	pathogenic	-2.475	Highly Destabilizing	0.136	N	0.584	neutral	None	None	None	None	N
I/H	0.8866	likely_pathogenic	0.883	pathogenic	-1.752	Destabilizing	0.864	D	0.569	neutral	None	None	None	None	N
I/K	0.8625	likely_pathogenic	0.8439	pathogenic	-1.425	Destabilizing	0.136	N	0.579	neutral	None	None	None	None	N
I/L	0.0865	likely_benign	0.0866	benign	-0.656	Destabilizing	None	N	0.112	neutral	N	0.425161288	None	None	N
I/M	0.1477	likely_benign	0.1494	benign	-0.581	Destabilizing	0.093	N	0.513	neutral	D	0.537332	None	None	N
I/N	0.7811	likely_pathogenic	0.7602	pathogenic	-1.527	Destabilizing	0.56	D	0.592	neutral	N	0.519880739	None	None	N
I/P	0.9742	likely_pathogenic	0.9677	pathogenic	-1.076	Destabilizing	0.628	D	0.598	neutral	None	None	None	None	N
I/Q	0.8245	likely_pathogenic	0.8158	pathogenic	-1.47	Destabilizing	0.628	D	0.594	neutral	None	None	None	None	N
I/R	0.8055	likely_pathogenic	0.7826	pathogenic	-1.088	Destabilizing	0.356	N	0.592	neutral	None	None	None	None	N
I/S	0.6966	likely_pathogenic	0.6868	pathogenic	-2.284	Highly Destabilizing	0.055	N	0.508	neutral	D	0.531406106	None	None	N
I/T	0.5315	ambiguous	0.5353	ambiguous	-1.987	Destabilizing	0.012	N	0.441	neutral	N	0.5148205	None	None	N
I/V	0.0646	likely_benign	0.0658	benign	-1.076	Destabilizing	None	N	0.139	neutral	N	0.357026567	None	None	N
I/W	0.9411	likely_pathogenic	0.931	pathogenic	-1.333	Destabilizing	0.864	D	0.57	neutral	None	None	None	None	N
I/Y	0.8186	likely_pathogenic	0.8015	pathogenic	-1.042	Destabilizing	0.356	N	0.569	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.