TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5043	15352;15353;15354	chr2:178734797;178734796;178734795	chr2:179599524;179599523;179599522
N2AB	4726	14401;14402;14403	chr2:178734797;178734796;178734795	chr2:179599524;179599523;179599522
N2A	3799	11620;11621;11622	chr2:178734797;178734796;178734795	chr2:179599524;179599523;179599522
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-33
• Domain position: 63
• Structural Position: 143
• Q(SASA): 0.6894
• 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
D/G	rs1578215701	None	0.811	N	0.385	0.208	0.208816687407	gnomAD-4.0.0	6.84213E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15945E-05	0
D/V	None	None	0.984	N	0.518	0.388	0.389283895039	gnomAD-4.0.0	6.84213E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9948E-07	0	0
D/Y	rs1345038643	-0.136	0.995	N	0.539	0.276	0.401753679984	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	9.19118E-04

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
D/A	0.1539	likely_benign	0.1406	benign	-0.266	Destabilizing	0.896	D	0.445	neutral	N	0.455787054	None	None	N
D/C	0.6028	likely_pathogenic	0.5888	pathogenic	0.241	Stabilizing	0.999	D	0.612	neutral	None	None	None	None	N
D/E	0.1634	likely_benign	0.1464	benign	-0.286	Destabilizing	0.026	N	0.253	neutral	N	0.441498178	None	None	N
D/F	0.6033	likely_pathogenic	0.5657	pathogenic	-0.424	Destabilizing	0.996	D	0.543	neutral	None	None	None	None	N
D/G	0.1482	likely_benign	0.1428	benign	-0.433	Destabilizing	0.811	D	0.385	neutral	N	0.454632747	None	None	N
D/H	0.2555	likely_benign	0.236	benign	-0.362	Destabilizing	0.984	D	0.395	neutral	N	0.458550768	None	None	N
D/I	0.5052	ambiguous	0.4475	ambiguous	0.117	Stabilizing	0.988	D	0.543	neutral	None	None	None	None	N
D/K	0.383	ambiguous	0.3269	benign	0.444	Stabilizing	0.851	D	0.377	neutral	None	None	None	None	N
D/L	0.4409	ambiguous	0.4139	ambiguous	0.117	Stabilizing	0.976	D	0.507	neutral	None	None	None	None	N
D/M	0.6071	likely_pathogenic	0.5742	pathogenic	0.366	Stabilizing	0.999	D	0.535	neutral	None	None	None	None	N
D/N	0.0733	likely_benign	0.0737	benign	0.261	Stabilizing	0.011	N	0.181	neutral	N	0.404791532	None	None	N
D/P	0.8511	likely_pathogenic	0.816	pathogenic	0.011	Stabilizing	0.988	D	0.393	neutral	None	None	None	None	N
D/Q	0.3295	likely_benign	0.2973	benign	0.252	Stabilizing	0.952	D	0.357	neutral	None	None	None	None	N
D/R	0.391	ambiguous	0.3469	ambiguous	0.468	Stabilizing	0.976	D	0.457	neutral	None	None	None	None	N
D/S	0.1109	likely_benign	0.1068	benign	0.152	Stabilizing	0.851	D	0.377	neutral	None	None	None	None	N
D/T	0.2751	likely_benign	0.2432	benign	0.277	Stabilizing	0.919	D	0.412	neutral	None	None	None	None	N
D/V	0.3062	likely_benign	0.2623	benign	0.011	Stabilizing	0.984	D	0.518	neutral	N	0.480359296	None	None	N
D/W	0.8745	likely_pathogenic	0.8654	pathogenic	-0.351	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	N
D/Y	0.2557	likely_benign	0.2295	benign	-0.196	Destabilizing	0.995	D	0.539	neutral	N	0.461055785	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.