TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30987	93184;93185;93186	chr2:178548667;178548666;178548665	chr2:179413394;179413393;179413392
N2AB	29346	88261;88262;88263	chr2:178548667;178548666;178548665	chr2:179413394;179413393;179413392
N2A	28419	85480;85481;85482	chr2:178548667;178548666;178548665	chr2:179413394;179413393;179413392
N2B	21922	65989;65990;65991	chr2:178548667;178548666;178548665	chr2:179413394;179413393;179413392
Novex-1	22047	66364;66365;66366	chr2:178548667;178548666;178548665	chr2:179413394;179413393;179413392
Novex-2	22114	66565;66566;66567	chr2:178548667;178548666;178548665	chr2:179413394;179413393;179413392
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-150
• Domain position: 61
• Structural Position: 145
• Q(SASA): 0.2495
• 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
N/S	rs2154147602	None	0.012	N	0.181	0.116	0.187945064343	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
N/Y	None	None	0.979	N	0.476	0.483	0.69386598177	gnomAD-4.0.0	1.08029E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.18125E-05	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
N/A	0.3794	ambiguous	0.3902	ambiguous	-0.391	Destabilizing	0.373	N	0.46	neutral	None	None	None	None	N
N/C	0.3108	likely_benign	0.3154	benign	0.372	Stabilizing	0.996	D	0.483	neutral	None	None	None	None	N
N/D	0.1185	likely_benign	0.1151	benign	-0.905	Destabilizing	0.684	D	0.395	neutral	N	0.488401903	None	None	N
N/E	0.5373	ambiguous	0.5479	ambiguous	-0.896	Destabilizing	0.742	D	0.363	neutral	None	None	None	None	N
N/F	0.5969	likely_pathogenic	0.6305	pathogenic	-0.579	Destabilizing	0.953	D	0.501	neutral	None	None	None	None	N
N/G	0.3374	likely_benign	0.337	benign	-0.637	Destabilizing	0.373	N	0.39	neutral	None	None	None	None	N
N/H	0.1328	likely_benign	0.1531	benign	-0.731	Destabilizing	0.979	D	0.426	neutral	N	0.506585019	None	None	N
N/I	0.3689	ambiguous	0.3866	ambiguous	0.192	Stabilizing	0.884	D	0.475	neutral	N	0.487631794	None	None	N
N/K	0.4772	ambiguous	0.5026	ambiguous	-0.141	Destabilizing	0.684	D	0.357	neutral	N	0.480550424	None	None	N
N/L	0.2911	likely_benign	0.3015	benign	0.192	Stabilizing	0.742	D	0.463	neutral	None	None	None	None	N
N/M	0.4417	ambiguous	0.4485	ambiguous	0.849	Stabilizing	0.996	D	0.464	neutral	None	None	None	None	N
N/P	0.8855	likely_pathogenic	0.877	pathogenic	0.026	Stabilizing	0.953	D	0.453	neutral	None	None	None	None	N
N/Q	0.4354	ambiguous	0.4643	ambiguous	-0.817	Destabilizing	0.91	D	0.401	neutral	None	None	None	None	N
N/R	0.4964	ambiguous	0.5285	ambiguous	-0.022	Destabilizing	0.742	D	0.397	neutral	None	None	None	None	N
N/S	0.0848	likely_benign	0.0851	benign	-0.453	Destabilizing	0.012	N	0.181	neutral	N	0.485534956	None	None	N
N/T	0.131	likely_benign	0.1284	benign	-0.302	Destabilizing	0.012	N	0.163	neutral	N	0.441994823	None	None	N
N/V	0.3573	ambiguous	0.3662	ambiguous	0.026	Stabilizing	0.742	D	0.474	neutral	None	None	None	None	N
N/W	0.8521	likely_pathogenic	0.8605	pathogenic	-0.504	Destabilizing	0.996	D	0.592	neutral	None	None	None	None	N
N/Y	0.2803	likely_benign	0.3038	benign	-0.232	Destabilizing	0.979	D	0.476	neutral	N	0.510508989	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.