TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14066	42421;42422;42423	chr2:178634585;178634584;178634583	chr2:179499312;179499311;179499310
N2AB	12425	37498;37499;37500	chr2:178634585;178634584;178634583	chr2:179499312;179499311;179499310
N2A	11498	34717;34718;34719	chr2:178634585;178634584;178634583	chr2:179499312;179499311;179499310
N2B	5001	15226;15227;15228	chr2:178634585;178634584;178634583	chr2:179499312;179499311;179499310
Novex-1	5126	15601;15602;15603	chr2:178634585;178634584;178634583	chr2:179499312;179499311;179499310
Novex-2	5193	15802;15803;15804	chr2:178634585;178634584;178634583	chr2:179499312;179499311;179499310
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-91
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.3675
• 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
P/L	None	None	0.999	N	0.701	0.441	0.49741755877	gnomAD-4.0.0	1.59226E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02608E-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
P/A	0.1855	likely_benign	0.2216	benign	-1.041	Destabilizing	0.996	D	0.629	neutral	N	0.478389547	None	None	N
P/C	0.8865	likely_pathogenic	0.924	pathogenic	-0.779	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
P/D	0.7566	likely_pathogenic	0.8347	pathogenic	-0.697	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
P/E	0.509	ambiguous	0.6079	pathogenic	-0.779	Destabilizing	0.998	D	0.654	neutral	None	None	None	None	N
P/F	0.8207	likely_pathogenic	0.8619	pathogenic	-1.039	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
P/G	0.6743	likely_pathogenic	0.7501	pathogenic	-1.247	Destabilizing	0.999	D	0.667	neutral	None	None	None	None	N
P/H	0.4916	ambiguous	0.5655	pathogenic	-0.756	Destabilizing	0.727	D	0.541	neutral	None	None	None	None	N
P/I	0.7032	likely_pathogenic	0.7524	pathogenic	-0.62	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
P/K	0.6681	likely_pathogenic	0.7552	pathogenic	-0.763	Destabilizing	0.998	D	0.691	prob.neutral	None	None	None	None	N
P/L	0.3077	likely_benign	0.3626	ambiguous	-0.62	Destabilizing	0.999	D	0.701	prob.neutral	N	0.453532463	None	None	N
P/M	0.6549	likely_pathogenic	0.704	pathogenic	-0.471	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
P/N	0.7168	likely_pathogenic	0.7906	pathogenic	-0.479	Destabilizing	0.998	D	0.696	prob.neutral	None	None	None	None	N
P/Q	0.3915	ambiguous	0.4802	ambiguous	-0.757	Destabilizing	0.999	D	0.691	prob.neutral	N	0.494939089	None	None	N
P/R	0.4822	ambiguous	0.5721	pathogenic	-0.204	Destabilizing	0.998	D	0.709	prob.delet.	N	0.498258773	None	None	N
P/S	0.3591	ambiguous	0.4416	ambiguous	-0.933	Destabilizing	0.999	D	0.649	neutral	N	0.493855024	None	None	N
P/T	0.3053	likely_benign	0.3695	ambiguous	-0.917	Destabilizing	0.999	D	0.695	prob.neutral	N	0.481147208	None	None	N
P/V	0.5433	ambiguous	0.5911	pathogenic	-0.725	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
P/W	0.894	likely_pathogenic	0.9244	pathogenic	-1.098	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
P/Y	0.798	likely_pathogenic	0.8454	pathogenic	-0.817	Destabilizing	0.998	D	0.73	prob.delet.	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.