TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35612	107059;107060;107061	chr2:178528917;178528916;178528915	chr2:179393644;179393643;179393642
N2AB	33971	102136;102137;102138	chr2:178528917;178528916;178528915	chr2:179393644;179393643;179393642
N2A	33044	99355;99356;99357	chr2:178528917;178528916;178528915	chr2:179393644;179393643;179393642
N2B	26547	79864;79865;79866	chr2:178528917;178528916;178528915	chr2:179393644;179393643;179393642
Novex-1	26672	80239;80240;80241	chr2:178528917;178528916;178528915	chr2:179393644;179393643;179393642
Novex-2	26739	80440;80441;80442	chr2:178528917;178528916;178528915	chr2:179393644;179393643;179393642
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-167
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.1654
• 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
F/S	rs762372340	-2.942	None	N	0.197	0.129	0.300784259202	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
F/S	rs762372340	-2.942	None	N	0.197	0.129	0.300784259202	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.82E-05	0	0	0	0	None	0	0	0	0	0
F/S	rs762372340	-2.942	None	N	0.197	0.129	0.300784259202	gnomAD-4.0.0	3.71768E-06	None	None	None	None	N	None	8.00683E-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
F/A	0.2309	likely_benign	0.3104	benign	-0.651	Destabilizing	0.007	N	0.307	neutral	None	None	None	None	N
F/C	0.2908	likely_benign	0.3279	benign	-0.199	Destabilizing	0.295	N	0.485	neutral	N	0.449422227	None	None	N
F/D	0.4512	ambiguous	0.5808	pathogenic	0.993	Stabilizing	0.038	N	0.495	neutral	None	None	None	None	N
F/E	0.5604	ambiguous	0.6703	pathogenic	0.961	Stabilizing	0.016	N	0.463	neutral	None	None	None	None	N
F/G	0.476	ambiguous	0.5648	pathogenic	-0.817	Destabilizing	0.016	N	0.398	neutral	None	None	None	None	N
F/H	0.4094	ambiguous	0.4921	ambiguous	0.325	Stabilizing	0.214	N	0.452	neutral	None	None	None	None	N
F/I	0.1232	likely_benign	0.1446	benign	-0.249	Destabilizing	0.012	N	0.375	neutral	N	0.447515286	None	None	N
F/K	0.5655	likely_pathogenic	0.6622	pathogenic	0.129	Stabilizing	0.016	N	0.449	neutral	None	None	None	None	N
F/L	0.5909	likely_pathogenic	0.6457	pathogenic	-0.249	Destabilizing	None	N	0.128	neutral	N	0.429622958	None	None	N
F/M	0.3621	ambiguous	0.4073	ambiguous	-0.228	Destabilizing	0.12	N	0.444	neutral	None	None	None	None	N
F/N	0.3065	likely_benign	0.41	ambiguous	0.199	Stabilizing	0.038	N	0.491	neutral	None	None	None	None	N
F/P	0.7203	likely_pathogenic	0.7836	pathogenic	-0.363	Destabilizing	0.072	N	0.541	neutral	None	None	None	None	N
F/Q	0.5092	ambiguous	0.6076	pathogenic	0.173	Stabilizing	0.072	N	0.546	neutral	None	None	None	None	N
F/R	0.4697	ambiguous	0.5593	ambiguous	0.466	Stabilizing	0.072	N	0.531	neutral	None	None	None	None	N
F/S	0.1473	likely_benign	0.2143	benign	-0.455	Destabilizing	None	N	0.197	neutral	N	0.404668586	None	None	N
F/T	0.2104	likely_benign	0.2998	benign	-0.393	Destabilizing	None	N	0.219	neutral	None	None	None	None	N
F/V	0.1225	likely_benign	0.1432	benign	-0.363	Destabilizing	0.005	N	0.347	neutral	N	0.447862002	None	None	N
F/W	0.4619	ambiguous	0.4894	ambiguous	-0.215	Destabilizing	0.356	N	0.459	neutral	None	None	None	None	N
F/Y	0.1422	likely_benign	0.1578	benign	-0.14	Destabilizing	None	N	0.165	neutral	N	0.449248869	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.