TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33544	100855;100856;100857	chr2:178536117;178536116;178536115	chr2:179400844;179400843;179400842
N2AB	31903	95932;95933;95934	chr2:178536117;178536116;178536115	chr2:179400844;179400843;179400842
N2A	30976	93151;93152;93153	chr2:178536117;178536116;178536115	chr2:179400844;179400843;179400842
N2B	24479	73660;73661;73662	chr2:178536117;178536116;178536115	chr2:179400844;179400843;179400842
Novex-1	24604	74035;74036;74037	chr2:178536117;178536116;178536115	chr2:179400844;179400843;179400842
Novex-2	24671	74236;74237;74238	chr2:178536117;178536116;178536115	chr2:179400844;179400843;179400842
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-158
• Domain position: 49
• Structural Position: 122
• Q(SASA): 0.3264
• Predicted PPI site: I

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
R/S	None	None	0.522	N	0.475	0.231	0.27855597813	gnomAD-4.0.0	6.84408E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	1.73551E-04	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
R/A	0.8453	likely_pathogenic	0.7531	pathogenic	-0.912	Destabilizing	0.592	D	0.449	neutral	None	None	None	None	I
R/C	0.5188	ambiguous	0.4103	ambiguous	-0.886	Destabilizing	0.998	D	0.511	neutral	None	None	None	None	I
R/D	0.9371	likely_pathogenic	0.874	pathogenic	-0.11	Destabilizing	0.875	D	0.505	neutral	None	None	None	None	I
R/E	0.7598	likely_pathogenic	0.6184	pathogenic	-0.013	Destabilizing	0.303	N	0.402	neutral	None	None	None	None	I
R/F	0.9393	likely_pathogenic	0.876	pathogenic	-0.948	Destabilizing	0.984	D	0.53	neutral	None	None	None	None	I
R/G	0.7533	likely_pathogenic	0.6298	pathogenic	-1.182	Destabilizing	0.841	D	0.509	neutral	D	0.52434406	None	None	I
R/H	0.2446	likely_benign	0.1774	benign	-1.397	Destabilizing	0.954	D	0.506	neutral	None	None	None	None	I
R/I	0.686	likely_pathogenic	0.5382	ambiguous	-0.195	Destabilizing	0.954	D	0.527	neutral	None	None	None	None	I
R/K	0.1519	likely_benign	0.1343	benign	-0.882	Destabilizing	None	N	0.117	neutral	N	0.433220624	None	None	I
R/L	0.7075	likely_pathogenic	0.5754	pathogenic	-0.195	Destabilizing	0.744	D	0.509	neutral	None	None	None	None	I
R/M	0.7425	likely_pathogenic	0.6184	pathogenic	-0.39	Destabilizing	0.979	D	0.541	neutral	N	0.504142146	None	None	I
R/N	0.8529	likely_pathogenic	0.7605	pathogenic	-0.291	Destabilizing	0.875	D	0.435	neutral	None	None	None	None	I
R/P	0.9863	likely_pathogenic	0.9763	pathogenic	-0.414	Destabilizing	0.934	D	0.535	neutral	None	None	None	None	I
R/Q	0.2092	likely_benign	0.1542	benign	-0.563	Destabilizing	0.722	D	0.451	neutral	None	None	None	None	I
R/S	0.8288	likely_pathogenic	0.722	pathogenic	-1.119	Destabilizing	0.522	D	0.475	neutral	N	0.462812812	None	None	I
R/T	0.619	likely_pathogenic	0.4638	ambiguous	-0.854	Destabilizing	0.841	D	0.498	neutral	N	0.450923737	None	None	I
R/V	0.749	likely_pathogenic	0.6266	pathogenic	-0.414	Destabilizing	0.678	D	0.532	neutral	None	None	None	None	I
R/W	0.7195	likely_pathogenic	0.5844	pathogenic	-0.605	Destabilizing	0.998	D	0.531	neutral	D	0.537524001	None	None	I
R/Y	0.8615	likely_pathogenic	0.7516	pathogenic	-0.29	Destabilizing	0.984	D	0.527	neutral	None	None	None	None	I

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.