TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9140	27643;27644;27645	chr2:178712504;178712503;178712502	chr2:179577231;179577230;179577229
N2AB	8823	26692;26693;26694	chr2:178712504;178712503;178712502	chr2:179577231;179577230;179577229
N2A	7896	23911;23912;23913	chr2:178712504;178712503;178712502	chr2:179577231;179577230;179577229
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: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-77
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.6766
• Predicted PPI site: I

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
P/L	rs371352652	0.199	0.669	N	0.509	0.331	None	gnomAD-2.1.1	7.13E-06	None	None	None	None	I	None	8.27E-05	0	None	0	0	None	0	None	0	0	0
P/L	rs371352652	0.199	0.669	N	0.509	0.331	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
P/L	rs371352652	0.199	0.669	N	0.509	0.331	None	gnomAD-4.0.0	1.31491E-05	None	None	None	None	I	None	4.82952E-05	0	None	0	0	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
P/A	0.0693	likely_benign	0.0716	benign	-0.383	Destabilizing	0.012	N	0.191	neutral	N	0.482717042	None	None	I
P/C	0.5342	ambiguous	0.5101	ambiguous	-0.636	Destabilizing	0.993	D	0.511	neutral	None	None	None	None	I
P/D	0.302	likely_benign	0.3365	benign	-0.393	Destabilizing	0.728	D	0.442	neutral	None	None	None	None	I
P/E	0.2094	likely_benign	0.2195	benign	-0.517	Destabilizing	0.067	N	0.229	neutral	None	None	None	None	I
P/F	0.399	ambiguous	0.4139	ambiguous	-0.713	Destabilizing	0.974	D	0.511	neutral	None	None	None	None	I
P/G	0.3034	likely_benign	0.3025	benign	-0.48	Destabilizing	0.728	D	0.483	neutral	None	None	None	None	I
P/H	0.1808	likely_benign	0.1853	benign	-0.107	Destabilizing	0.989	D	0.496	neutral	N	0.520206226	None	None	I
P/I	0.2583	likely_benign	0.2699	benign	-0.281	Destabilizing	0.949	D	0.521	neutral	None	None	None	None	I
P/K	0.2203	likely_benign	0.2528	benign	-0.428	Destabilizing	0.029	N	0.171	neutral	None	None	None	None	I
P/L	0.1141	likely_benign	0.1204	benign	-0.281	Destabilizing	0.669	D	0.509	neutral	N	0.493770633	None	None	I
P/M	0.271	likely_benign	0.276	benign	-0.422	Destabilizing	0.991	D	0.491	neutral	None	None	None	None	I
P/N	0.2617	likely_benign	0.2742	benign	-0.164	Destabilizing	0.915	D	0.495	neutral	None	None	None	None	I
P/Q	0.1313	likely_benign	0.1349	benign	-0.411	Destabilizing	0.842	D	0.467	neutral	None	None	None	None	I
P/R	0.1545	likely_benign	0.1722	benign	0.074	Stabilizing	0.012	N	0.365	neutral	N	0.520263605	None	None	I
P/S	0.1075	likely_benign	0.117	benign	-0.464	Destabilizing	0.454	N	0.425	neutral	N	0.48609763	None	None	I
P/T	0.0997	likely_benign	0.1039	benign	-0.492	Destabilizing	0.801	D	0.441	neutral	D	0.529824451	None	None	I
P/V	0.1775	likely_benign	0.1779	benign	-0.283	Destabilizing	0.728	D	0.48	neutral	None	None	None	None	I
P/W	0.6033	likely_pathogenic	0.6376	pathogenic	-0.792	Destabilizing	0.998	D	0.577	neutral	None	None	None	None	I
P/Y	0.3807	ambiguous	0.3948	ambiguous	-0.496	Destabilizing	0.991	D	0.513	neutral	None	None	None	None	I

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.