TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7231	21916;21917;21918	chr2:178723316;178723315;178723314	chr2:179588043;179588042;179588041
N2AB	6914	20965;20966;20967	chr2:178723316;178723315;178723314	chr2:179588043;179588042;179588041
N2A	5987	18184;18185;18186	chr2:178723316;178723315;178723314	chr2:179588043;179588042;179588041
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-57
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.3418
• 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
A/E	None	None	0.012	N	0.398	0.162	0.132336055621	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
A/T	rs1486491329	-0.343	None	N	0.169	0.064	0.0297737177859	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.32E-05	None	0	0	0
A/T	rs1486491329	-0.343	None	N	0.169	0.064	0.0297737177859	gnomAD-4.0.0	2.74132E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.6581E-05	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
A/C	0.3294	likely_benign	0.3101	benign	-0.827	Destabilizing	0.356	N	0.435	neutral	None	None	None	None	N
A/D	0.2205	likely_benign	0.2254	benign	-0.265	Destabilizing	0.072	N	0.423	neutral	None	None	None	None	N
A/E	0.1542	likely_benign	0.1518	benign	-0.246	Destabilizing	0.012	N	0.398	neutral	N	0.49399415	None	None	N
A/F	0.1653	likely_benign	0.1722	benign	-0.599	Destabilizing	0.214	N	0.497	neutral	None	None	None	None	N
A/G	0.1409	likely_benign	0.1418	benign	-0.903	Destabilizing	0.024	N	0.317	neutral	N	0.487331262	None	None	N
A/H	0.2428	likely_benign	0.23	benign	-0.999	Destabilizing	0.001	N	0.378	neutral	None	None	None	None	N
A/I	0.1034	likely_benign	0.0991	benign	0.084	Stabilizing	0.006	N	0.412	neutral	None	None	None	None	N
A/K	0.159	likely_benign	0.1584	benign	-0.697	Destabilizing	None	N	0.244	neutral	None	None	None	None	N
A/L	0.0991	likely_benign	0.095	benign	0.084	Stabilizing	0.016	N	0.407	neutral	None	None	None	None	N
A/M	0.1233	likely_benign	0.1224	benign	-0.148	Destabilizing	0.214	N	0.423	neutral	None	None	None	None	N
A/N	0.1517	likely_benign	0.1561	benign	-0.555	Destabilizing	0.072	N	0.418	neutral	None	None	None	None	N
A/P	0.5481	ambiguous	0.6112	pathogenic	-0.099	Destabilizing	0.106	N	0.445	neutral	N	0.475810373	None	None	N
A/Q	0.1791	likely_benign	0.166	benign	-0.574	Destabilizing	0.038	N	0.443	neutral	None	None	None	None	N
A/R	0.1372	likely_benign	0.1305	benign	-0.589	Destabilizing	None	N	0.298	neutral	None	None	None	None	N
A/S	0.0859	likely_benign	0.0842	benign	-1.054	Destabilizing	0.001	N	0.225	neutral	N	0.464191318	None	None	N
A/T	0.0618	likely_benign	0.0613	benign	-0.905	Destabilizing	None	N	0.169	neutral	N	0.432041614	None	None	N
A/V	0.0719	likely_benign	0.0663	benign	-0.099	Destabilizing	None	N	0.153	neutral	N	0.467829056	None	None	N
A/W	0.4912	ambiguous	0.5039	ambiguous	-0.968	Destabilizing	0.864	D	0.481	neutral	None	None	None	None	N
A/Y	0.2412	likely_benign	0.2526	benign	-0.485	Destabilizing	0.214	N	0.505	neutral	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.