TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18569	55930;55931;55932	chr2:178601292;178601291;178601290	chr2:179466019;179466018;179466017
N2AB	16928	51007;51008;51009	chr2:178601292;178601291;178601290	chr2:179466019;179466018;179466017
N2A	16001	48226;48227;48228	chr2:178601292;178601291;178601290	chr2:179466019;179466018;179466017
N2B	9504	28735;28736;28737	chr2:178601292;178601291;178601290	chr2:179466019;179466018;179466017
Novex-1	9629	29110;29111;29112	chr2:178601292;178601291;178601290	chr2:179466019;179466018;179466017
Novex-2	9696	29311;29312;29313	chr2:178601292;178601291;178601290	chr2:179466019;179466018;179466017
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Fn3-22
• Domain position: 91
• Structural Position: 125
• Q(SASA): 0.4134
• 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
Q/P	None	None	0.915	N	0.495	0.26	0.256283259241	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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
Q/A	0.3098	likely_benign	0.3167	benign	-0.016	Destabilizing	0.594	D	0.314	neutral	None	None	None	None	N
Q/C	0.8441	likely_pathogenic	0.8021	pathogenic	-0.183	Destabilizing	0.998	D	0.43	neutral	None	None	None	None	N
Q/D	0.6022	likely_pathogenic	0.5965	pathogenic	-0.011	Destabilizing	0.594	D	0.337	neutral	None	None	None	None	N
Q/E	0.1127	likely_benign	0.1097	benign	-0.054	Destabilizing	0.01	N	0.056	neutral	N	0.341717893	None	None	N
Q/F	0.8314	likely_pathogenic	0.8256	pathogenic	-0.436	Destabilizing	0.994	D	0.521	neutral	None	None	None	None	N
Q/G	0.4355	ambiguous	0.4155	ambiguous	-0.121	Destabilizing	0.745	D	0.405	neutral	None	None	None	None	N
Q/H	0.4466	ambiguous	0.4362	ambiguous	0.146	Stabilizing	0.991	D	0.373	neutral	N	0.501583765	None	None	N
Q/I	0.5022	ambiguous	0.5254	ambiguous	0.16	Stabilizing	0.981	D	0.585	neutral	None	None	None	None	N
Q/K	0.2243	likely_benign	0.212	benign	0.042	Stabilizing	0.688	D	0.38	neutral	N	0.457523557	None	None	N
Q/L	0.2416	likely_benign	0.2411	benign	0.16	Stabilizing	0.915	D	0.447	neutral	N	0.500196898	None	None	N
Q/M	0.4695	ambiguous	0.5036	ambiguous	0.002	Stabilizing	0.994	D	0.372	neutral	None	None	None	None	N
Q/N	0.4426	ambiguous	0.4877	ambiguous	-0.288	Destabilizing	0.876	D	0.337	neutral	None	None	None	None	N
Q/P	0.5501	ambiguous	0.4344	ambiguous	0.125	Stabilizing	0.915	D	0.495	neutral	N	0.449058789	None	None	N
Q/R	0.2554	likely_benign	0.2191	benign	0.238	Stabilizing	0.842	D	0.41	neutral	N	0.445037049	None	None	N
Q/S	0.3113	likely_benign	0.3391	benign	-0.264	Destabilizing	0.216	N	0.123	neutral	None	None	None	None	N
Q/T	0.2592	likely_benign	0.2957	benign	-0.182	Destabilizing	0.78	D	0.413	neutral	None	None	None	None	N
Q/V	0.3283	likely_benign	0.36	ambiguous	0.125	Stabilizing	0.935	D	0.452	neutral	None	None	None	None	N
Q/W	0.8364	likely_pathogenic	0.7826	pathogenic	-0.534	Destabilizing	0.998	D	0.473	neutral	None	None	None	None	N
Q/Y	0.6986	likely_pathogenic	0.6948	pathogenic	-0.222	Destabilizing	0.994	D	0.479	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.