TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7251	21976;21977;21978	chr2:178723256;178723255;178723254	chr2:179587983;179587982;179587981
N2AB	6934	21025;21026;21027	chr2:178723256;178723255;178723254	chr2:179587983;179587982;179587981
N2A	6007	18244;18245;18246	chr2:178723256;178723255;178723254	chr2:179587983;179587982;179587981
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: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-57
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.1343
• 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/I	rs1387731794	0.872	0.106	N	0.791	0.125	0.241078983079	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	9.98E-05	0	None	0	None	0	0	0
S/I	rs1387731794	0.872	0.106	N	0.791	0.125	0.241078983079	gnomAD-4.0.0	1.59182E-06	None	None	None	None	N	None	0	0	None	4.76917E-05	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	0.0807	likely_benign	0.0779	benign	-0.755	Destabilizing	0.007	N	0.449	neutral	None	None	None	None	N
S/C	0.0858	likely_benign	0.0799	benign	-0.484	Destabilizing	None	N	0.533	neutral	N	0.259439573	None	None	N
S/D	0.8998	likely_pathogenic	0.9023	pathogenic	-1.729	Destabilizing	0.016	N	0.561	neutral	None	None	None	None	N
S/E	0.9455	likely_pathogenic	0.9468	pathogenic	-1.478	Destabilizing	0.072	N	0.587	neutral	None	None	None	None	N
S/F	0.8208	likely_pathogenic	0.8334	pathogenic	-0.383	Destabilizing	0.628	D	0.804	deleterious	None	None	None	None	N
S/G	0.0528	likely_benign	0.0515	benign	-1.182	Destabilizing	None	N	0.307	neutral	N	0.4086466	None	None	N
S/H	0.9093	likely_pathogenic	0.9124	pathogenic	-1.462	Destabilizing	0.214	N	0.759	deleterious	None	None	None	None	N
S/I	0.3147	likely_benign	0.3305	benign	0.358	Stabilizing	0.106	N	0.791	deleterious	N	0.451973303	None	None	N
S/K	0.9879	likely_pathogenic	0.9884	pathogenic	-0.191	Destabilizing	0.038	N	0.587	neutral	None	None	None	None	N
S/L	0.3978	ambiguous	0.4071	ambiguous	0.358	Stabilizing	0.072	N	0.727	prob.delet.	None	None	None	None	N
S/M	0.4378	ambiguous	0.4661	ambiguous	0.111	Stabilizing	0.628	D	0.775	deleterious	None	None	None	None	N
S/N	0.4423	ambiguous	0.4598	ambiguous	-1.088	Destabilizing	None	N	0.377	neutral	N	0.453533528	None	None	N
S/P	0.9659	likely_pathogenic	0.9646	pathogenic	0.02	Stabilizing	0.136	N	0.761	deleterious	None	None	None	None	N
S/Q	0.9399	likely_pathogenic	0.94	pathogenic	-0.652	Destabilizing	0.214	N	0.679	prob.neutral	None	None	None	None	N
S/R	0.9786	likely_pathogenic	0.9794	pathogenic	-0.761	Destabilizing	0.055	N	0.734	prob.delet.	N	0.490974408	None	None	N
S/T	0.1235	likely_benign	0.1371	benign	-0.648	Destabilizing	0.024	N	0.592	neutral	N	0.46082486	None	None	N
S/V	0.2683	likely_benign	0.2813	benign	0.02	Stabilizing	0.072	N	0.735	prob.delet.	None	None	None	None	N
S/W	0.9368	likely_pathogenic	0.9365	pathogenic	-0.826	Destabilizing	0.864	D	0.819	deleterious	None	None	None	None	N
S/Y	0.7906	likely_pathogenic	0.7931	pathogenic	-0.325	Destabilizing	0.628	D	0.806	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.