TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26176	78751;78752;78753	chr2:178567606;178567605;178567604	chr2:179432333;179432332;179432331
N2AB	24535	73828;73829;73830	chr2:178567606;178567605;178567604	chr2:179432333;179432332;179432331
N2A	23608	71047;71048;71049	chr2:178567606;178567605;178567604	chr2:179432333;179432332;179432331
N2B	17111	51556;51557;51558	chr2:178567606;178567605;178567604	chr2:179432333;179432332;179432331
Novex-1	17236	51931;51932;51933	chr2:178567606;178567605;178567604	chr2:179432333;179432332;179432331
Novex-2	17303	52132;52133;52134	chr2:178567606;178567605;178567604	chr2:179432333;179432332;179432331
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-78
• Domain position: 89
• Structural Position: 121
• Q(SASA): 0.1564
• 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
S/P	None	None	0.994	D	0.819	0.73	0.584954716481	gnomAD-4.0.0	6.85091E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00426E-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
S/A	0.43	ambiguous	0.4477	ambiguous	-0.776	Destabilizing	0.873	D	0.804	deleterious	D	0.554838709	None	None	N
S/C	0.5696	likely_pathogenic	0.6233	pathogenic	-0.931	Destabilizing	0.999	D	0.821	deleterious	D	0.55175129	None	None	N
S/D	0.9957	likely_pathogenic	0.9944	pathogenic	-1.761	Destabilizing	0.996	D	0.856	deleterious	None	None	None	None	N
S/E	0.9966	likely_pathogenic	0.9963	pathogenic	-1.664	Destabilizing	0.957	D	0.846	deleterious	None	None	None	None	N
S/F	0.9945	likely_pathogenic	0.9949	pathogenic	-0.729	Destabilizing	0.935	D	0.862	deleterious	D	0.574463901	None	None	N
S/G	0.4257	ambiguous	0.4313	ambiguous	-1.08	Destabilizing	0.957	D	0.81	deleterious	None	None	None	None	N
S/H	0.9931	likely_pathogenic	0.9928	pathogenic	-1.479	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
S/I	0.9878	likely_pathogenic	0.988	pathogenic	-0.045	Destabilizing	0.987	D	0.857	deleterious	None	None	None	None	N
S/K	0.9993	likely_pathogenic	0.9992	pathogenic	-0.847	Destabilizing	0.957	D	0.839	deleterious	None	None	None	None	N
S/L	0.9399	likely_pathogenic	0.9448	pathogenic	-0.045	Destabilizing	0.916	D	0.881	deleterious	None	None	None	None	N
S/M	0.9729	likely_pathogenic	0.9736	pathogenic	-0.009	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
S/N	0.9764	likely_pathogenic	0.9751	pathogenic	-1.271	Destabilizing	0.996	D	0.851	deleterious	None	None	None	None	N
S/P	0.9928	likely_pathogenic	0.9911	pathogenic	-0.256	Destabilizing	0.994	D	0.819	deleterious	D	0.574210412	None	None	N
S/Q	0.9946	likely_pathogenic	0.9944	pathogenic	-1.305	Destabilizing	0.996	D	0.829	deleterious	None	None	None	None	N
S/R	0.9978	likely_pathogenic	0.9977	pathogenic	-0.843	Destabilizing	0.987	D	0.819	deleterious	None	None	None	None	N
S/T	0.7111	likely_pathogenic	0.6704	pathogenic	-0.999	Destabilizing	0.944	D	0.835	deleterious	D	0.541707977	None	None	N
S/V	0.9681	likely_pathogenic	0.967	pathogenic	-0.256	Destabilizing	0.987	D	0.854	deleterious	None	None	None	None	N
S/W	0.9954	likely_pathogenic	0.9952	pathogenic	-0.893	Destabilizing	0.073	N	0.814	deleterious	None	None	None	None	N
S/Y	0.9926	likely_pathogenic	0.9932	pathogenic	-0.519	Destabilizing	0.935	D	0.862	deleterious	D	0.562854106	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.