TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18852	56779;56780;56781	chr2:178599239;178599238;178599237	chr2:179463966;179463965;179463964
N2AB	17211	51856;51857;51858	chr2:178599239;178599238;178599237	chr2:179463966;179463965;179463964
N2A	16284	49075;49076;49077	chr2:178599239;178599238;178599237	chr2:179463966;179463965;179463964
N2B	9787	29584;29585;29586	chr2:178599239;178599238;178599237	chr2:179463966;179463965;179463964
Novex-1	9912	29959;29960;29961	chr2:178599239;178599238;178599237	chr2:179463966;179463965;179463964
Novex-2	9979	30160;30161;30162	chr2:178599239;178599238;178599237	chr2:179463966;179463965;179463964
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-24
• Domain position: 69
• Structural Position: 100
• Q(SASA): 0.4123
• 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
G/V	rs1283827826	-0.451	0.89	D	0.763	0.384	0.577534042849	gnomAD-2.1.1	1.5E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.55958E-04	None	0	0	0
G/V	rs1283827826	-0.451	0.89	D	0.763	0.384	0.577534042849	gnomAD-4.0.0	5.29891E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	5.35447E-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
G/A	0.4075	ambiguous	0.5214	ambiguous	-0.393	Destabilizing	0.032	N	0.348	neutral	N	0.484115258	None	None	N
G/C	0.4625	ambiguous	0.5572	ambiguous	-0.74	Destabilizing	0.992	D	0.818	deleterious	D	0.540949692	None	None	N
G/D	0.2218	likely_benign	0.3712	ambiguous	-1.021	Destabilizing	0.032	N	0.423	neutral	N	0.477176271	None	None	N
G/E	0.4476	ambiguous	0.5929	pathogenic	-1.18	Destabilizing	0.915	D	0.685	prob.neutral	None	None	None	None	N
G/F	0.8069	likely_pathogenic	0.8797	pathogenic	-1.103	Destabilizing	0.994	D	0.778	deleterious	None	None	None	None	N
G/H	0.5562	ambiguous	0.6798	pathogenic	-0.777	Destabilizing	0.994	D	0.753	deleterious	None	None	None	None	N
G/I	0.8125	likely_pathogenic	0.8952	pathogenic	-0.443	Destabilizing	0.956	D	0.782	deleterious	None	None	None	None	N
G/K	0.7046	likely_pathogenic	0.7761	pathogenic	-1.05	Destabilizing	0.956	D	0.687	prob.neutral	None	None	None	None	N
G/L	0.7812	likely_pathogenic	0.8707	pathogenic	-0.443	Destabilizing	0.915	D	0.762	deleterious	None	None	None	None	N
G/M	0.7765	likely_pathogenic	0.8477	pathogenic	-0.356	Destabilizing	0.998	D	0.797	deleterious	None	None	None	None	N
G/N	0.2429	likely_benign	0.3332	benign	-0.569	Destabilizing	0.076	N	0.355	neutral	None	None	None	None	N
G/P	0.9795	likely_pathogenic	0.9898	pathogenic	-0.391	Destabilizing	0.978	D	0.754	deleterious	None	None	None	None	N
G/Q	0.5577	ambiguous	0.6596	pathogenic	-0.898	Destabilizing	0.956	D	0.755	deleterious	None	None	None	None	N
G/R	0.6337	likely_pathogenic	0.7197	pathogenic	-0.533	Destabilizing	0.942	D	0.754	deleterious	N	0.521577989	None	None	N
G/S	0.2048	likely_benign	0.2688	benign	-0.66	Destabilizing	0.698	D	0.578	neutral	N	0.490343002	None	None	N
G/T	0.4666	ambiguous	0.5645	pathogenic	-0.764	Destabilizing	0.956	D	0.669	neutral	None	None	None	None	N
G/V	0.7049	likely_pathogenic	0.8258	pathogenic	-0.391	Destabilizing	0.89	D	0.763	deleterious	D	0.529086408	None	None	N
G/W	0.6924	likely_pathogenic	0.7743	pathogenic	-1.297	Destabilizing	0.998	D	0.78	deleterious	None	None	None	None	N
G/Y	0.5744	likely_pathogenic	0.7223	pathogenic	-0.949	Destabilizing	0.998	D	0.779	deleterious	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.