TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9061	27406;27407;27408	chr2:178712844;178712843;178712842	chr2:179577571;179577570;179577569
N2AB	8744	26455;26456;26457	chr2:178712844;178712843;178712842	chr2:179577571;179577570;179577569
N2A	7817	23674;23675;23676	chr2:178712844;178712843;178712842	chr2:179577571;179577570;179577569
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: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-76
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.517
• 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
P/A	rs772373852	0.079	0.016	N	0.207	0.117	0.208000267992	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
P/A	rs772373852	0.079	0.016	N	0.207	0.117	0.208000267992	gnomAD-4.0.0	2.73692E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.63811E-05	0
P/Q	None	None	0.016	N	0.224	0.143	0.363751660372	gnomAD-4.0.0	2.05269E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	3.47826E-05	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	0.0675	likely_benign	0.0696	benign	-0.391	Destabilizing	0.016	N	0.207	neutral	N	0.517319301	None	None	N
P/C	0.5066	ambiguous	0.4889	ambiguous	-0.627	Destabilizing	0.977	D	0.479	neutral	None	None	None	None	N
P/D	0.3806	ambiguous	0.3921	ambiguous	-0.373	Destabilizing	0.617	D	0.378	neutral	None	None	None	None	N
P/E	0.2035	likely_benign	0.2131	benign	-0.5	Destabilizing	0.447	N	0.348	neutral	None	None	None	None	N
P/F	0.3875	ambiguous	0.3766	ambiguous	-0.739	Destabilizing	0.92	D	0.475	neutral	None	None	None	None	N
P/G	0.2598	likely_benign	0.269	benign	-0.487	Destabilizing	0.447	N	0.379	neutral	None	None	None	None	N
P/H	0.1574	likely_benign	0.1581	benign	-0.116	Destabilizing	0.977	D	0.445	neutral	None	None	None	None	N
P/I	0.2785	likely_benign	0.2717	benign	-0.292	Destabilizing	0.85	D	0.479	neutral	None	None	None	None	N
P/K	0.1893	likely_benign	0.1976	benign	-0.397	Destabilizing	0.447	N	0.333	neutral	None	None	None	None	N
P/L	0.1034	likely_benign	0.1041	benign	-0.292	Destabilizing	0.549	D	0.407	neutral	N	0.491058206	None	None	N
P/M	0.2657	likely_benign	0.2609	benign	-0.392	Destabilizing	0.992	D	0.445	neutral	None	None	None	None	N
P/N	0.3075	likely_benign	0.3049	benign	-0.13	Destabilizing	0.739	D	0.418	neutral	None	None	None	None	N
P/Q	0.1166	likely_benign	0.1206	benign	-0.385	Destabilizing	0.016	N	0.224	neutral	N	0.479166344	None	None	N
P/R	0.1217	likely_benign	0.1253	benign	0.111	Stabilizing	0.681	D	0.429	neutral	D	0.527170935	None	None	N
P/S	0.1025	likely_benign	0.1015	benign	-0.438	Destabilizing	0.004	N	0.221	neutral	N	0.442434753	None	None	N
P/T	0.0893	likely_benign	0.0935	benign	-0.468	Destabilizing	0.379	N	0.331	neutral	N	0.470893578	None	None	N
P/V	0.1961	likely_benign	0.1952	benign	-0.292	Destabilizing	0.617	D	0.388	neutral	None	None	None	None	N
P/W	0.4647	ambiguous	0.4706	ambiguous	-0.812	Destabilizing	0.992	D	0.576	neutral	None	None	None	None	N
P/Y	0.3528	ambiguous	0.355	ambiguous	-0.511	Destabilizing	0.972	D	0.475	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.