TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7246	21961;21962;21963	chr2:178723271;178723270;178723269	chr2:179587998;179587997;179587996
N2AB	6929	21010;21011;21012	chr2:178723271;178723270;178723269	chr2:179587998;179587997;179587996
N2A	6002	18229;18230;18231	chr2:178723271;178723270;178723269	chr2:179587998;179587997;179587996
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: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-57
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.5336
• 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
S/F	rs1477073298	-0.839	0.989	N	0.427	0.381	0.560757523052	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14758E-04	0	None	0	0	None	0	None	0	0	0
S/F	rs1477073298	-0.839	0.989	N	0.427	0.381	0.560757523052	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
S/F	rs1477073298	-0.839	0.989	N	0.427	0.381	0.560757523052	gnomAD-4.0.0	3.84442E-06	None	None	None	None	N	None	5.06637E-05	0	None	0	0	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
S/A	0.0756	likely_benign	0.0779	benign	-0.754	Destabilizing	0.625	D	0.327	neutral	N	0.51333398	None	None	N
S/C	0.1655	likely_benign	0.1688	benign	-0.551	Destabilizing	0.997	D	0.386	neutral	N	0.471255609	None	None	N
S/D	0.3896	ambiguous	0.433	ambiguous	-0.467	Destabilizing	0.915	D	0.26	neutral	None	None	None	None	N
S/E	0.5122	ambiguous	0.5484	ambiguous	-0.44	Destabilizing	0.842	D	0.262	neutral	None	None	None	None	N
S/F	0.2852	likely_benign	0.3215	benign	-0.84	Destabilizing	0.989	D	0.427	neutral	N	0.47100212	None	None	N
S/G	0.1057	likely_benign	0.1172	benign	-1.036	Destabilizing	0.688	D	0.293	neutral	None	None	None	None	N
S/H	0.3428	ambiguous	0.3797	ambiguous	-1.466	Destabilizing	0.998	D	0.386	neutral	None	None	None	None	N
S/I	0.233	likely_benign	0.2649	benign	-0.103	Destabilizing	0.949	D	0.43	neutral	None	None	None	None	N
S/K	0.5929	likely_pathogenic	0.6442	pathogenic	-0.745	Destabilizing	0.842	D	0.266	neutral	None	None	None	None	N
S/L	0.1277	likely_benign	0.1429	benign	-0.103	Destabilizing	0.842	D	0.349	neutral	None	None	None	None	N
S/M	0.2451	likely_benign	0.2695	benign	0.176	Stabilizing	0.998	D	0.39	neutral	None	None	None	None	N
S/N	0.1195	likely_benign	0.1358	benign	-0.826	Destabilizing	0.915	D	0.349	neutral	None	None	None	None	N
S/P	0.0717	likely_benign	0.0743	benign	-0.285	Destabilizing	0.002	N	0.144	neutral	N	0.407782596	None	None	N
S/Q	0.4408	ambiguous	0.4763	ambiguous	-0.925	Destabilizing	0.974	D	0.389	neutral	None	None	None	None	N
S/R	0.5169	ambiguous	0.5677	pathogenic	-0.67	Destabilizing	0.974	D	0.405	neutral	None	None	None	None	N
S/T	0.0978	likely_benign	0.1037	benign	-0.795	Destabilizing	0.051	N	0.133	neutral	N	0.447068916	None	None	N
S/V	0.2263	likely_benign	0.2477	benign	-0.285	Destabilizing	0.842	D	0.342	neutral	None	None	None	None	N
S/W	0.4002	ambiguous	0.4552	ambiguous	-0.842	Destabilizing	0.998	D	0.574	neutral	None	None	None	None	N
S/Y	0.2047	likely_benign	0.2318	benign	-0.566	Destabilizing	0.989	D	0.425	neutral	N	0.47100212	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.