TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30100	90523;90524;90525	chr2:178552602;178552601;178552600	chr2:179417329;179417328;179417327
N2AB	28459	85600;85601;85602	chr2:178552602;178552601;178552600	chr2:179417329;179417328;179417327
N2A	27532	82819;82820;82821	chr2:178552602;178552601;178552600	chr2:179417329;179417328;179417327
N2B	21035	63328;63329;63330	chr2:178552602;178552601;178552600	chr2:179417329;179417328;179417327
Novex-1	21160	63703;63704;63705	chr2:178552602;178552601;178552600	chr2:179417329;179417328;179417327
Novex-2	21227	63904;63905;63906	chr2:178552602;178552601;178552600	chr2:179417329;179417328;179417327
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-107
• Domain position: 71
• Structural Position: 105
• Q(SASA): 0.2523
• 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/K	rs762287310	0.322	0.852	N	0.567	0.264	0.246773566709	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
E/K	rs762287310	0.322	0.852	N	0.567	0.264	0.246773566709	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs762287310	0.322	0.852	N	0.567	0.264	0.246773566709	gnomAD-4.0.0	6.57229E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47011E-05	0	0
E/Q	rs762287310	None	0.31	N	0.299	0.202	0.242825505644	gnomAD-4.0.0	1.36837E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79886E-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
E/A	0.2787	likely_benign	0.2409	benign	-0.418	Destabilizing	0.92	D	0.533	neutral	N	0.444735978	None	None	N
E/C	0.8461	likely_pathogenic	0.8384	pathogenic	-0.027	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	N
E/D	0.2516	likely_benign	0.1964	benign	-1.381	Destabilizing	0.035	N	0.32	neutral	N	0.481888857	None	None	N
E/F	0.7456	likely_pathogenic	0.6849	pathogenic	0.208	Stabilizing	0.964	D	0.614	neutral	None	None	None	None	N
E/G	0.4503	ambiguous	0.387	ambiguous	-0.903	Destabilizing	0.959	D	0.524	neutral	N	0.514385278	None	None	N
E/H	0.5872	likely_pathogenic	0.5184	ambiguous	-0.016	Destabilizing	0.982	D	0.533	neutral	None	None	None	None	N
E/I	0.4101	ambiguous	0.3918	ambiguous	0.949	Stabilizing	0.991	D	0.611	neutral	None	None	None	None	N
E/K	0.5162	ambiguous	0.4753	ambiguous	-0.537	Destabilizing	0.852	D	0.567	neutral	N	0.442522393	None	None	N
E/L	0.5	ambiguous	0.4633	ambiguous	0.949	Stabilizing	0.939	D	0.527	neutral	None	None	None	None	N
E/M	0.5285	ambiguous	0.5055	ambiguous	1.55	Stabilizing	0.999	D	0.595	neutral	None	None	None	None	N
E/N	0.4778	ambiguous	0.4043	ambiguous	-1.103	Destabilizing	0.939	D	0.493	neutral	None	None	None	None	N
E/P	0.9783	likely_pathogenic	0.97	pathogenic	0.514	Stabilizing	0.997	D	0.535	neutral	None	None	None	None	N
E/Q	0.2129	likely_benign	0.1918	benign	-0.745	Destabilizing	0.31	N	0.299	neutral	N	0.411180765	None	None	N
E/R	0.6108	likely_pathogenic	0.5625	ambiguous	-0.507	Destabilizing	0.939	D	0.503	neutral	None	None	None	None	N
E/S	0.3399	likely_benign	0.2904	benign	-1.65	Destabilizing	0.939	D	0.543	neutral	None	None	None	None	N
E/T	0.3284	likely_benign	0.3009	benign	-1.198	Destabilizing	0.969	D	0.471	neutral	None	None	None	None	N
E/V	0.272	likely_benign	0.2554	benign	0.514	Stabilizing	0.92	D	0.542	neutral	N	0.435423062	None	None	N
E/W	0.9202	likely_pathogenic	0.896	pathogenic	0.175	Stabilizing	0.998	D	0.651	neutral	None	None	None	None	N
E/Y	0.6584	likely_pathogenic	0.5798	pathogenic	0.459	Stabilizing	0.321	N	0.546	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.