TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9453	28582;28583;28584	chr2:178710740;178710739;178710738	chr2:179575467;179575466;179575465
N2AB	9136	27631;27632;27633	chr2:178710740;178710739;178710738	chr2:179575467;179575466;179575465
N2A	8209	24850;24851;24852	chr2:178710740;178710739;178710738	chr2:179575467;179575466;179575465
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-80
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.3441
• 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
H/Q	None	None	0.007	None	0.371	0.08	0.26547132957	gnomAD-4.0.0	6.84184E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99433E-07	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
H/A	0.4629	ambiguous	0.5823	pathogenic	-0.593	Destabilizing	0.228	N	0.474	neutral	None	None	None	None	N
H/C	0.2409	likely_benign	0.3113	benign	0.091	Stabilizing	0.005	N	0.499	neutral	None	None	None	None	N
H/D	0.5009	ambiguous	0.5619	ambiguous	-0.441	Destabilizing	0.351	N	0.523	neutral	None	None	None	None	N
H/E	0.4428	ambiguous	0.5294	ambiguous	-0.374	Destabilizing	0.264	N	0.411	neutral	None	None	None	None	N
H/F	0.347	ambiguous	0.4288	ambiguous	0.135	Stabilizing	0.264	N	0.577	neutral	None	None	None	None	N
H/G	0.5346	ambiguous	0.6487	pathogenic	-0.922	Destabilizing	0.418	N	0.557	neutral	None	None	None	None	N
H/I	0.412	ambiguous	0.4945	ambiguous	0.297	Stabilizing	0.264	N	0.576	neutral	None	None	None	None	N
H/K	0.2327	likely_benign	0.3166	benign	-0.411	Destabilizing	0.264	N	0.502	neutral	None	None	None	None	N
H/L	0.1946	likely_benign	0.2309	benign	0.297	Stabilizing	0.002	N	0.502	neutral	None	None	None	None	N
H/M	0.5906	likely_pathogenic	0.7027	pathogenic	0.217	Stabilizing	0.716	D	0.595	neutral	None	None	None	None	N
H/N	0.2103	likely_benign	0.2418	benign	-0.34	Destabilizing	0.351	N	0.459	neutral	None	None	None	None	N
H/P	0.8077	likely_pathogenic	0.8659	pathogenic	0.022	Stabilizing	0.002	N	0.498	neutral	None	None	None	None	N
H/Q	0.2054	likely_benign	0.2574	benign	-0.176	Destabilizing	0.007	N	0.371	neutral	None	None	None	None	N
H/R	0.0913	likely_benign	0.1049	benign	-0.735	Destabilizing	0.213	N	0.454	neutral	None	None	None	None	N
H/S	0.3323	likely_benign	0.4201	ambiguous	-0.41	Destabilizing	0.418	N	0.488	neutral	None	None	None	None	N
H/T	0.3841	ambiguous	0.4876	ambiguous	-0.248	Destabilizing	0.418	N	0.547	neutral	None	None	None	None	N
H/V	0.358	ambiguous	0.4314	ambiguous	0.022	Stabilizing	0.264	N	0.543	neutral	None	None	None	None	N
H/W	0.4058	ambiguous	0.4806	ambiguous	0.254	Stabilizing	0.951	D	0.612	neutral	None	None	None	None	N
H/Y	0.1167	likely_benign	0.1303	benign	0.545	Stabilizing	0.002	N	0.354	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.