TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7101	21526;21527;21528	chr2:178723958;178723957;178723956	chr2:179588685;179588684;179588683
N2AB	6784	20575;20576;20577	chr2:178723958;178723957;178723956	chr2:179588685;179588684;179588683
N2A	5857	17794;17795;17796	chr2:178723958;178723957;178723956	chr2:179588685;179588684;179588683
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-55
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.0629
• 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/S	None	None	1.0	D	0.873	0.772	0.898077514524	gnomAD-4.0.0	1.59191E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85969E-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
L/A	0.9093	likely_pathogenic	0.9111	pathogenic	-2.312	Highly Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
L/C	0.9177	likely_pathogenic	0.9326	pathogenic	-1.548	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
L/D	0.9993	likely_pathogenic	0.9992	pathogenic	-3.102	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/E	0.994	likely_pathogenic	0.9937	pathogenic	-2.771	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
L/F	0.5245	ambiguous	0.4966	ambiguous	-1.413	Destabilizing	1.0	D	0.813	deleterious	D	0.541942375	None	None	N
L/G	0.9819	likely_pathogenic	0.981	pathogenic	-2.921	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
L/H	0.9767	likely_pathogenic	0.9762	pathogenic	-2.849	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
L/I	0.2289	likely_benign	0.2305	benign	-0.475	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
L/K	0.9904	likely_pathogenic	0.9889	pathogenic	-1.664	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
L/M	0.2975	likely_benign	0.3175	benign	-0.721	Destabilizing	1.0	D	0.8	deleterious	D	0.539322256	None	None	N
L/N	0.9947	likely_pathogenic	0.9943	pathogenic	-2.426	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
L/P	0.9964	likely_pathogenic	0.9954	pathogenic	-1.079	Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	N
L/Q	0.9648	likely_pathogenic	0.9627	pathogenic	-2.014	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
L/R	0.9717	likely_pathogenic	0.9673	pathogenic	-1.947	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
L/S	0.9805	likely_pathogenic	0.981	pathogenic	-2.924	Highly Destabilizing	1.0	D	0.873	deleterious	D	0.588572593	None	None	N
L/T	0.957	likely_pathogenic	0.9596	pathogenic	-2.419	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
L/V	0.251	likely_benign	0.2698	benign	-1.079	Destabilizing	0.999	D	0.693	prob.neutral	D	0.54877923	None	None	N
L/W	0.9323	likely_pathogenic	0.9289	pathogenic	-1.828	Destabilizing	1.0	D	0.863	deleterious	D	0.588572593	None	None	N
L/Y	0.9444	likely_pathogenic	0.9426	pathogenic	-1.573	Destabilizing	1.0	D	0.855	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.