TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15536	46831;46832;46833	chr2:178619711;178619710;178619709	chr2:179484438;179484437;179484436
N2AB	13895	41908;41909;41910	chr2:178619711;178619710;178619709	chr2:179484438;179484437;179484436
N2A	12968	39127;39128;39129	chr2:178619711;178619710;178619709	chr2:179484438;179484437;179484436
N2B	6471	19636;19637;19638	chr2:178619711;178619710;178619709	chr2:179484438;179484437;179484436
Novex-1	6596	20011;20012;20013	chr2:178619711;178619710;178619709	chr2:179484438;179484437;179484436
Novex-2	6663	20212;20213;20214	chr2:178619711;178619710;178619709	chr2:179484438;179484437;179484436
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-107
• Domain position: 57
• Structural Position: 138
• Q(SASA): 0.0829
• 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
L/Q	rs775884428	-2.643	1.0	D	0.912	0.896	0.892716174367	gnomAD-2.1.1	2.42E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.96181E-04	None	0	0	0
L/Q	rs775884428	-2.643	1.0	D	0.912	0.896	0.892716174367	gnomAD-4.0.0	8.9016E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.39221E-04	1.65837E-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
L/A	0.9856	likely_pathogenic	0.9886	pathogenic	-2.302	Highly Destabilizing	0.999	D	0.756	deleterious	None	None	None	None	N
L/C	0.9519	likely_pathogenic	0.9713	pathogenic	-1.513	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
L/D	0.9998	likely_pathogenic	0.9999	pathogenic	-3.191	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
L/E	0.9987	likely_pathogenic	0.9987	pathogenic	-2.876	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
L/F	0.6371	likely_pathogenic	0.7461	pathogenic	-1.442	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
L/G	0.9965	likely_pathogenic	0.9975	pathogenic	-2.875	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
L/H	0.9943	likely_pathogenic	0.9942	pathogenic	-2.786	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
L/I	0.3984	ambiguous	0.4472	ambiguous	-0.571	Destabilizing	0.999	D	0.641	neutral	D	0.643873549	None	None	N
L/K	0.9963	likely_pathogenic	0.9963	pathogenic	-1.748	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
L/M	0.398	ambiguous	0.4287	ambiguous	-0.802	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
L/N	0.9985	likely_pathogenic	0.9985	pathogenic	-2.508	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
L/P	0.9992	likely_pathogenic	0.9993	pathogenic	-1.141	Destabilizing	1.0	D	0.911	deleterious	D	0.642931647	None	None	N
L/Q	0.9919	likely_pathogenic	0.9909	pathogenic	-2.119	Highly Destabilizing	1.0	D	0.912	deleterious	D	0.642931647	None	None	N
L/R	0.9923	likely_pathogenic	0.9933	pathogenic	-1.991	Destabilizing	1.0	D	0.906	deleterious	D	0.642931647	None	None	N
L/S	0.9985	likely_pathogenic	0.9985	pathogenic	-2.945	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
L/T	0.9954	likely_pathogenic	0.9955	pathogenic	-2.466	Highly Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
L/V	0.5753	likely_pathogenic	0.6496	pathogenic	-1.141	Destabilizing	0.999	D	0.641	neutral	D	0.64290376	None	None	N
L/W	0.9706	likely_pathogenic	0.9768	pathogenic	-1.849	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
L/Y	0.9709	likely_pathogenic	0.9783	pathogenic	-1.608	Destabilizing	1.0	D	0.862	deleterious	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.