TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6048	18367;18368;18369	chr2:178730258;178730257;178730256	chr2:179594985;179594984;179594983
N2AB	5731	17416;17417;17418	chr2:178730258;178730257;178730256	chr2:179594985;179594984;179594983
N2A	4804	14635;14636;14637	chr2:178730258;178730257;178730256	chr2:179594985;179594984;179594983
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-44
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.408
• 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	rs1400771825	-0.329	0.989	N	0.479	0.453	0.275641507738	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	5.62E-05	None	0	None	0	0	0
D/G	rs1400771825	-0.329	0.989	N	0.479	0.453	0.275641507738	gnomAD-4.0.0	3.18501E-06	None	None	None	None	N	None	0	0	None	0	5.56143E-05	None	0	0	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
D/A	0.376	ambiguous	0.2936	benign	-0.006	Destabilizing	0.994	D	0.539	neutral	N	0.470752311	None	None	N
D/C	0.8271	likely_pathogenic	0.7384	pathogenic	0.039	Stabilizing	1.0	D	0.672	neutral	None	None	None	None	N
D/E	0.255	likely_benign	0.208	benign	-0.217	Destabilizing	0.973	D	0.419	neutral	N	0.456886051	None	None	N
D/F	0.8123	likely_pathogenic	0.7377	pathogenic	-0.088	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	N
D/G	0.1445	likely_benign	0.1225	benign	-0.144	Destabilizing	0.989	D	0.479	neutral	N	0.457923414	None	None	N
D/H	0.5526	ambiguous	0.4458	ambiguous	0.331	Stabilizing	0.998	D	0.555	neutral	N	0.489363545	None	None	N
D/I	0.8002	likely_pathogenic	0.6867	pathogenic	0.294	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
D/K	0.6714	likely_pathogenic	0.5338	ambiguous	0.473	Stabilizing	0.992	D	0.517	neutral	None	None	None	None	N
D/L	0.709	likely_pathogenic	0.6166	pathogenic	0.294	Stabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	N
D/M	0.8679	likely_pathogenic	0.7952	pathogenic	0.212	Stabilizing	1.0	D	0.665	neutral	None	None	None	None	N
D/N	0.1358	likely_benign	0.1153	benign	0.286	Stabilizing	0.333	N	0.235	neutral	N	0.456227117	None	None	N
D/P	0.9612	likely_pathogenic	0.9349	pathogenic	0.215	Stabilizing	1.0	D	0.554	neutral	None	None	None	None	N
D/Q	0.5739	likely_pathogenic	0.4651	ambiguous	0.286	Stabilizing	0.999	D	0.505	neutral	None	None	None	None	N
D/R	0.6776	likely_pathogenic	0.5577	ambiguous	0.654	Stabilizing	0.999	D	0.614	neutral	None	None	None	None	N
D/S	0.2775	likely_benign	0.2263	benign	0.172	Stabilizing	0.992	D	0.442	neutral	None	None	None	None	N
D/T	0.6606	likely_pathogenic	0.5381	ambiguous	0.28	Stabilizing	0.992	D	0.517	neutral	None	None	None	None	N
D/V	0.5718	likely_pathogenic	0.4505	ambiguous	0.215	Stabilizing	0.999	D	0.691	prob.neutral	N	0.468221097	None	None	N
D/W	0.9397	likely_pathogenic	0.9027	pathogenic	-0.036	Destabilizing	1.0	D	0.662	neutral	None	None	None	None	N
D/Y	0.3704	ambiguous	0.2979	benign	0.142	Stabilizing	0.999	D	0.672	neutral	N	0.484844095	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.