TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14565	43918;43919;43920	chr2:178632201;178632200;178632199	chr2:179496928;179496927;179496926
N2AB	12924	38995;38996;38997	chr2:178632201;178632200;178632199	chr2:179496928;179496927;179496926
N2A	11997	36214;36215;36216	chr2:178632201;178632200;178632199	chr2:179496928;179496927;179496926
N2B	5500	16723;16724;16725	chr2:178632201;178632200;178632199	chr2:179496928;179496927;179496926
Novex-1	5625	17098;17099;17100	chr2:178632201;178632200;178632199	chr2:179496928;179496927;179496926
Novex-2	5692	17299;17300;17301	chr2:178632201;178632200;178632199	chr2:179496928;179496927;179496926
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Ig-96
• Domain position: 69
• Structural Position: 153
• Q(SASA): 0.5911
• 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	rs1357364341	None	0.856	D	0.518	0.301	0.41337360676	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
Q/P	rs1357364341	None	0.856	D	0.518	0.301	0.41337360676	gnomAD-4.0.0	6.57644E-06	None	None	None	None	N	None	0	6.55738E-05	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
Q/A	0.2669	likely_benign	0.2341	benign	-0.465	Destabilizing	0.187	N	0.3	neutral	None	None	None	None	N
Q/C	0.7483	likely_pathogenic	0.6902	pathogenic	0.076	Stabilizing	0.965	D	0.493	neutral	None	None	None	None	N
Q/D	0.3906	ambiguous	0.3453	ambiguous	-0.915	Destabilizing	0.561	D	0.362	neutral	None	None	None	None	N
Q/E	0.0904	likely_benign	0.0779	benign	-0.844	Destabilizing	0.285	N	0.337	neutral	N	0.479502863	None	None	N
Q/F	0.6915	likely_pathogenic	0.6219	pathogenic	-0.259	Destabilizing	0.561	D	0.565	neutral	None	None	None	None	N
Q/G	0.3843	ambiguous	0.339	benign	-0.803	Destabilizing	0.561	D	0.469	neutral	None	None	None	None	N
Q/H	0.2651	likely_benign	0.2267	benign	-0.865	Destabilizing	0.003	N	0.229	neutral	D	0.593679776	None	None	N
Q/I	0.3182	likely_benign	0.2684	benign	0.386	Stabilizing	0.209	N	0.424	neutral	None	None	None	None	N
Q/K	0.095	likely_benign	0.0821	benign	-0.385	Destabilizing	0.285	N	0.371	neutral	N	0.491908951	None	None	N
Q/L	0.1326	likely_benign	0.1141	benign	0.386	Stabilizing	None	N	0.262	neutral	N	0.508228296	None	None	N
Q/M	0.3346	likely_benign	0.2997	benign	0.888	Stabilizing	0.047	N	0.168	neutral	None	None	None	None	N
Q/N	0.294	likely_benign	0.2639	benign	-0.857	Destabilizing	0.561	D	0.364	neutral	None	None	None	None	N
Q/P	0.2099	likely_benign	0.1838	benign	0.134	Stabilizing	0.856	D	0.518	neutral	D	0.548472214	None	None	N
Q/R	0.1241	likely_benign	0.1112	benign	-0.323	Destabilizing	0.491	N	0.359	neutral	D	0.590515243	None	None	N
Q/S	0.309	likely_benign	0.2836	benign	-0.876	Destabilizing	0.209	N	0.367	neutral	None	None	None	None	N
Q/T	0.2059	likely_benign	0.1799	benign	-0.626	Destabilizing	0.007	N	0.216	neutral	None	None	None	None	N
Q/V	0.2242	likely_benign	0.1933	benign	0.134	Stabilizing	0.209	N	0.31	neutral	None	None	None	None	N
Q/W	0.5243	ambiguous	0.4855	ambiguous	-0.199	Destabilizing	0.991	D	0.501	neutral	None	None	None	None	N
Q/Y	0.4987	ambiguous	0.4527	ambiguous	0.054	Stabilizing	0.39	N	0.523	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.