TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7674	23245;23246;23247	chr2:178720999;178720998;178720997	chr2:179585726;179585725;179585724
N2AB	7357	22294;22295;22296	chr2:178720999;178720998;178720997	chr2:179585726;179585725;179585724
N2A	6430	19513;19514;19515	chr2:178720999;178720998;178720997	chr2:179585726;179585725;179585724
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-61
• Domain position: 67
• Structural Position: 148
• Q(SASA): 0.3882
• 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/A	None	None	0.789	N	0.418	0.15	0.297375071883	gnomAD-4.0.0	1.59359E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43423E-05	0
E/D	rs865791908	None	0.002	N	0.169	0.065	0.0846915920261	gnomAD-4.0.0	1.59352E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41313E-03	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
E/A	0.1155	likely_benign	0.1408	benign	-0.065	Destabilizing	0.789	D	0.418	neutral	N	0.488630324	None	None	N
E/C	0.8325	likely_pathogenic	0.904	pathogenic	0.222	Stabilizing	0.998	D	0.609	neutral	None	None	None	None	N
E/D	0.094	likely_benign	0.095	benign	-0.127	Destabilizing	0.002	N	0.169	neutral	N	0.46450267	None	None	N
E/F	0.6621	likely_pathogenic	0.781	pathogenic	-0.22	Destabilizing	0.995	D	0.537	neutral	None	None	None	None	N
E/G	0.1232	likely_benign	0.158	benign	-0.171	Destabilizing	0.962	D	0.42	neutral	N	0.45840482	None	None	N
E/H	0.3944	ambiguous	0.524	ambiguous	0.126	Stabilizing	0.993	D	0.364	neutral	None	None	None	None	N
E/I	0.3459	ambiguous	0.4393	ambiguous	0.154	Stabilizing	0.989	D	0.53	neutral	None	None	None	None	N
E/K	0.1089	likely_benign	0.1534	benign	0.634	Stabilizing	0.038	N	0.135	neutral	N	0.508640236	None	None	N
E/L	0.3401	ambiguous	0.4474	ambiguous	0.154	Stabilizing	0.968	D	0.448	neutral	None	None	None	None	N
E/M	0.4043	ambiguous	0.504	ambiguous	0.21	Stabilizing	0.984	D	0.491	neutral	None	None	None	None	N
E/N	0.1992	likely_benign	0.2523	benign	0.489	Stabilizing	0.667	D	0.409	neutral	None	None	None	None	N
E/P	0.6769	likely_pathogenic	0.7874	pathogenic	0.099	Stabilizing	0.933	D	0.385	neutral	None	None	None	None	N
E/Q	0.1352	likely_benign	0.1752	benign	0.49	Stabilizing	0.832	D	0.441	neutral	N	0.461380561	None	None	N
E/R	0.1961	likely_benign	0.291	benign	0.661	Stabilizing	0.821	D	0.412	neutral	None	None	None	None	N
E/S	0.1414	likely_benign	0.1771	benign	0.35	Stabilizing	0.832	D	0.4	neutral	None	None	None	None	N
E/T	0.1807	likely_benign	0.2248	benign	0.444	Stabilizing	0.933	D	0.41	neutral	None	None	None	None	N
E/V	0.2047	likely_benign	0.2598	benign	0.099	Stabilizing	0.943	D	0.399	neutral	N	0.478777254	None	None	N
E/W	0.794	likely_pathogenic	0.8931	pathogenic	-0.201	Destabilizing	1.0	D	0.652	neutral	None	None	None	None	N
E/Y	0.5455	ambiguous	0.6827	pathogenic	-0.003	Destabilizing	0.998	D	0.499	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.