TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23127	69604;69605;69606	chr2:178576956;178576955;178576954	chr2:179441683;179441682;179441681
N2AB	21486	64681;64682;64683	chr2:178576956;178576955;178576954	chr2:179441683;179441682;179441681
N2A	20559	61900;61901;61902	chr2:178576956;178576955;178576954	chr2:179441683;179441682;179441681
N2B	14062	42409;42410;42411	chr2:178576956;178576955;178576954	chr2:179441683;179441682;179441681
Novex-1	14187	42784;42785;42786	chr2:178576956;178576955;178576954	chr2:179441683;179441682;179441681
Novex-2	14254	42985;42986;42987	chr2:178576956;178576955;178576954	chr2:179441683;179441682;179441681
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: Fn3-55
• Domain position: 88
• Structural Position: 122
• Q(SASA): 0.3054
• 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/E	rs953796748	-0.186	0.002	N	0.22	0.097	0.0954503805726	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.66223E-04
Q/E	rs953796748	-0.186	0.002	N	0.22	0.097	0.0954503805726	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
Q/E	rs953796748	-0.186	0.002	N	0.22	0.097	0.0954503805726	gnomAD-4.0.0	5.12706E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.18322E-06	0	2.84608E-05

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	0.1881	likely_benign	0.1656	benign	-0.712	Destabilizing	0.134	N	0.464	neutral	None	None	None	None	N
Q/C	0.57	likely_pathogenic	0.487	ambiguous	-0.079	Destabilizing	0.984	D	0.661	prob.neutral	None	None	None	None	N
Q/D	0.3596	ambiguous	0.3316	benign	-0.102	Destabilizing	0.272	N	0.401	neutral	None	None	None	None	N
Q/E	0.0765	likely_benign	0.0731	benign	0.017	Stabilizing	0.002	N	0.22	neutral	N	0.33998431	None	None	N
Q/F	0.5536	ambiguous	0.4705	ambiguous	-0.33	Destabilizing	0.724	D	0.661	prob.neutral	None	None	None	None	N
Q/G	0.3704	ambiguous	0.3354	benign	-1.07	Destabilizing	0.428	N	0.585	neutral	None	None	None	None	N
Q/H	0.2182	likely_benign	0.1973	benign	-0.595	Destabilizing	0.002	N	0.227	neutral	N	0.455582116	None	None	N
Q/I	0.2308	likely_benign	0.1981	benign	0.206	Stabilizing	0.272	N	0.654	prob.neutral	None	None	None	None	N
Q/K	0.1595	likely_benign	0.1382	benign	-0.166	Destabilizing	0.22	N	0.409	neutral	N	0.455888761	None	None	N
Q/L	0.0984	likely_benign	0.0918	benign	0.206	Stabilizing	0.22	N	0.606	neutral	N	0.459179782	None	None	N
Q/M	0.2507	likely_benign	0.2193	benign	0.431	Stabilizing	0.842	D	0.468	neutral	None	None	None	None	N
Q/N	0.2676	likely_benign	0.2443	benign	-0.755	Destabilizing	0.428	N	0.419	neutral	None	None	None	None	N
Q/P	0.1364	likely_benign	0.1257	benign	-0.07	Destabilizing	0.8	D	0.589	neutral	N	0.43822572	None	None	N
Q/R	0.1745	likely_benign	0.1548	benign	-0.074	Destabilizing	0.361	N	0.399	neutral	N	0.474455879	None	None	N
Q/S	0.2106	likely_benign	0.1865	benign	-0.945	Destabilizing	0.272	N	0.401	neutral	None	None	None	None	N
Q/T	0.1579	likely_benign	0.1405	benign	-0.62	Destabilizing	0.428	N	0.511	neutral	None	None	None	None	N
Q/V	0.1475	likely_benign	0.1329	benign	-0.07	Destabilizing	0.002	N	0.491	neutral	None	None	None	None	N
Q/W	0.5552	ambiguous	0.5043	ambiguous	-0.157	Destabilizing	0.984	D	0.656	prob.neutral	None	None	None	None	N
Q/Y	0.4045	ambiguous	0.3555	ambiguous	0.056	Stabilizing	0.724	D	0.589	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.