TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32116	96571;96572;96573	chr2:178543627;178543626;178543625	chr2:179408354;179408353;179408352
N2AB	30475	91648;91649;91650	chr2:178543627;178543626;178543625	chr2:179408354;179408353;179408352
N2A	29548	88867;88868;88869	chr2:178543627;178543626;178543625	chr2:179408354;179408353;179408352
N2B	23051	69376;69377;69378	chr2:178543627;178543626;178543625	chr2:179408354;179408353;179408352
Novex-1	23176	69751;69752;69753	chr2:178543627;178543626;178543625	chr2:179408354;179408353;179408352
Novex-2	23243	69952;69953;69954	chr2:178543627;178543626;178543625	chr2:179408354;179408353;179408352
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: Fn3-122
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.2861
• 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/G	None	None	0.975	N	0.533	0.361	0.378498632473	gnomAD-4.0.0	6.90551E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.01367E-07	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
E/A	0.2333	likely_benign	0.2272	benign	-0.658	Destabilizing	0.96	D	0.502	neutral	N	0.503685495	None	None	N
E/C	0.9147	likely_pathogenic	0.9106	pathogenic	-0.269	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	N
E/D	0.0992	likely_benign	0.098	benign	-0.643	Destabilizing	0.002	N	0.135	neutral	N	0.423165841	None	None	N
E/F	0.8605	likely_pathogenic	0.8544	pathogenic	-0.321	Destabilizing	0.998	D	0.656	neutral	None	None	None	None	N
E/G	0.2791	likely_benign	0.2779	benign	-0.92	Destabilizing	0.975	D	0.533	neutral	N	0.513094412	None	None	N
E/H	0.6492	likely_pathogenic	0.6515	pathogenic	-0.264	Destabilizing	0.998	D	0.534	neutral	None	None	None	None	N
E/I	0.6493	likely_pathogenic	0.6363	pathogenic	0.023	Stabilizing	0.997	D	0.661	neutral	None	None	None	None	N
E/K	0.4979	ambiguous	0.4865	ambiguous	-0.032	Destabilizing	0.956	D	0.491	neutral	N	0.517558869	None	None	N
E/L	0.6636	likely_pathogenic	0.6527	pathogenic	0.023	Stabilizing	0.99	D	0.644	neutral	None	None	None	None	N
E/M	0.6621	likely_pathogenic	0.6501	pathogenic	0.22	Stabilizing	0.995	D	0.583	neutral	None	None	None	None	N
E/N	0.3214	likely_benign	0.3159	benign	-0.475	Destabilizing	0.862	D	0.496	neutral	None	None	None	None	N
E/P	0.965	likely_pathogenic	0.9627	pathogenic	-0.183	Destabilizing	0.977	D	0.577	neutral	None	None	None	None	N
E/Q	0.2895	likely_benign	0.2941	benign	-0.409	Destabilizing	0.969	D	0.515	neutral	N	0.503552209	None	None	N
E/R	0.6241	likely_pathogenic	0.6214	pathogenic	0.238	Stabilizing	0.995	D	0.537	neutral	None	None	None	None	N
E/S	0.2903	likely_benign	0.2948	benign	-0.658	Destabilizing	0.939	D	0.463	neutral	None	None	None	None	N
E/T	0.3452	ambiguous	0.3553	ambiguous	-0.443	Destabilizing	0.977	D	0.53	neutral	None	None	None	None	N
E/V	0.4133	ambiguous	0.3997	ambiguous	-0.183	Destabilizing	0.994	D	0.531	neutral	N	0.47842313	None	None	N
E/W	0.9468	likely_pathogenic	0.944	pathogenic	-0.083	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	N
E/Y	0.7325	likely_pathogenic	0.7209	pathogenic	-0.066	Destabilizing	0.999	D	0.619	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.