TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19985	60178;60179;60180	chr2:178591866;178591865;178591864	chr2:179456593;179456592;179456591
N2AB	18344	55255;55256;55257	chr2:178591866;178591865;178591864	chr2:179456593;179456592;179456591
N2A	17417	52474;52475;52476	chr2:178591866;178591865;178591864	chr2:179456593;179456592;179456591
N2B	10920	32983;32984;32985	chr2:178591866;178591865;178591864	chr2:179456593;179456592;179456591
Novex-1	11045	33358;33359;33360	chr2:178591866;178591865;178591864	chr2:179456593;179456592;179456591
Novex-2	11112	33559;33560;33561	chr2:178591866;178591865;178591864	chr2:179456593;179456592;179456591
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: Fn3-33
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.4961
• 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/Y	None	None	0.014	N	0.283	0.326	0.218112801441	gnomAD-4.0.0	1.59394E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8608E-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
H/A	0.7691	likely_pathogenic	0.7619	pathogenic	-0.31	Destabilizing	0.86	D	0.645	neutral	None	None	None	None	N
H/C	0.3487	ambiguous	0.3681	ambiguous	0.603	Stabilizing	0.998	D	0.796	deleterious	None	None	None	None	N
H/D	0.7716	likely_pathogenic	0.7536	pathogenic	-0.487	Destabilizing	0.99	D	0.667	neutral	N	0.472709227	None	None	N
H/E	0.6926	likely_pathogenic	0.6842	pathogenic	-0.39	Destabilizing	0.926	D	0.523	neutral	None	None	None	None	N
H/F	0.5552	ambiguous	0.5687	pathogenic	0.95	Stabilizing	0.915	D	0.661	neutral	None	None	None	None	N
H/G	0.761	likely_pathogenic	0.7656	pathogenic	-0.684	Destabilizing	0.926	D	0.662	neutral	None	None	None	None	N
H/I	0.6764	likely_pathogenic	0.6763	pathogenic	0.719	Stabilizing	0.956	D	0.787	deleterious	None	None	None	None	N
H/K	0.3998	ambiguous	0.405	ambiguous	-0.153	Destabilizing	0.978	D	0.651	neutral	None	None	None	None	N
H/L	0.3543	ambiguous	0.3623	ambiguous	0.719	Stabilizing	0.698	D	0.675	prob.neutral	N	0.480501991	None	None	N
H/M	0.7729	likely_pathogenic	0.7758	pathogenic	0.552	Stabilizing	0.998	D	0.764	deleterious	None	None	None	None	N
H/N	0.3941	ambiguous	0.3728	ambiguous	-0.259	Destabilizing	0.904	D	0.541	neutral	N	0.486811887	None	None	N
H/P	0.9074	likely_pathogenic	0.924	pathogenic	0.398	Stabilizing	0.99	D	0.783	deleterious	N	0.490372268	None	None	N
H/Q	0.3931	ambiguous	0.3636	ambiguous	None	Stabilizing	0.97	D	0.569	neutral	N	0.439364657	None	None	N
H/R	0.15	likely_benign	0.1458	benign	-0.889	Destabilizing	0.97	D	0.547	neutral	N	0.428147586	None	None	N
H/S	0.6433	likely_pathogenic	0.6328	pathogenic	-0.118	Destabilizing	0.926	D	0.651	neutral	None	None	None	None	N
H/T	0.6706	likely_pathogenic	0.651	pathogenic	0.081	Stabilizing	0.978	D	0.7	prob.neutral	None	None	None	None	N
H/V	0.6144	likely_pathogenic	0.6136	pathogenic	0.398	Stabilizing	0.956	D	0.706	prob.neutral	None	None	None	None	N
H/W	0.5899	likely_pathogenic	0.6136	pathogenic	1.137	Stabilizing	0.994	D	0.767	deleterious	None	None	None	None	N
H/Y	0.2478	likely_benign	0.251	benign	1.236	Stabilizing	0.014	N	0.283	neutral	N	0.50626444	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.