TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19421	58486;58487;58488	chr2:178594132;178594131;178594130	chr2:179458859;179458858;179458857
N2AB	17780	53563;53564;53565	chr2:178594132;178594131;178594130	chr2:179458859;179458858;179458857
N2A	16853	50782;50783;50784	chr2:178594132;178594131;178594130	chr2:179458859;179458858;179458857
N2B	10356	31291;31292;31293	chr2:178594132;178594131;178594130	chr2:179458859;179458858;179458857
Novex-1	10481	31666;31667;31668	chr2:178594132;178594131;178594130	chr2:179458859;179458858;179458857
Novex-2	10548	31867;31868;31869	chr2:178594132;178594131;178594130	chr2:179458859;179458858;179458857
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-118
• Domain position: 31
• Structural Position: 49
• Q(SASA): 0.2313
• 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
F/S	None	None	0.003	N	0.345	0.254	0.250579442822	gnomAD-4.0.0	3.18394E-06	None	None	None	None	N	None	0	0	None	0	5.56576E-05	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
F/A	0.3985	ambiguous	0.2993	benign	-2.298	Highly Destabilizing	0.055	N	0.491	neutral	None	None	None	None	N
F/C	0.2193	likely_benign	0.1674	benign	-1.06	Destabilizing	0.822	D	0.554	neutral	N	0.469204921	None	None	N
F/D	0.7528	likely_pathogenic	0.6899	pathogenic	-1.128	Destabilizing	0.22	N	0.587	neutral	None	None	None	None	N
F/E	0.5775	likely_pathogenic	0.4963	ambiguous	-1.059	Destabilizing	0.22	N	0.569	neutral	None	None	None	None	N
F/G	0.6301	likely_pathogenic	0.5435	ambiguous	-2.622	Highly Destabilizing	0.124	N	0.542	neutral	None	None	None	None	N
F/H	0.2682	likely_benign	0.2302	benign	-0.925	Destabilizing	0.667	D	0.532	neutral	None	None	None	None	N
F/I	0.1601	likely_benign	0.1263	benign	-1.327	Destabilizing	0.042	N	0.404	neutral	N	0.464580028	None	None	N
F/K	0.3357	likely_benign	0.2931	benign	-1.032	Destabilizing	0.124	N	0.549	neutral	None	None	None	None	N
F/L	0.5754	likely_pathogenic	0.4626	ambiguous	-1.327	Destabilizing	None	N	0.179	neutral	N	0.391119632	None	None	N
F/M	0.3062	likely_benign	0.2488	benign	-0.969	Destabilizing	0.497	N	0.499	neutral	None	None	None	None	N
F/N	0.4307	ambiguous	0.365	ambiguous	-0.981	Destabilizing	0.124	N	0.601	neutral	None	None	None	None	N
F/P	0.9933	likely_pathogenic	0.9914	pathogenic	-1.645	Destabilizing	0.667	D	0.61	neutral	None	None	None	None	N
F/Q	0.3356	likely_benign	0.2883	benign	-1.149	Destabilizing	0.497	N	0.601	neutral	None	None	None	None	N
F/R	0.2797	likely_benign	0.2414	benign	-0.322	Destabilizing	0.497	N	0.613	neutral	None	None	None	None	N
F/S	0.2724	likely_benign	0.1958	benign	-1.796	Destabilizing	0.003	N	0.345	neutral	N	0.426504429	None	None	N
F/T	0.2693	likely_benign	0.2105	benign	-1.638	Destabilizing	0.002	N	0.329	neutral	None	None	None	None	N
F/V	0.161	likely_benign	0.1267	benign	-1.645	Destabilizing	0.042	N	0.449	neutral	N	0.483165789	None	None	N
F/W	0.3431	ambiguous	0.3002	benign	-0.518	Destabilizing	0.958	D	0.516	neutral	None	None	None	None	N
F/Y	0.1071	likely_benign	0.1014	benign	-0.677	Destabilizing	0.301	N	0.434	neutral	N	0.41555393	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.