TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8651	26176;26177;26178	chr2:178715235;178715234;178715233	chr2:179579962;179579961;179579960
N2AB	8334	25225;25226;25227	chr2:178715235;178715234;178715233	chr2:179579962;179579961;179579960
N2A	7407	22444;22445;22446	chr2:178715235;178715234;178715233	chr2:179579962;179579961;179579960
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: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-72
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.5319
• Predicted PPI site: I

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
P/L	rs368758220	0.138	0.003	N	0.307	0.195	None	gnomAD-2.1.1	4.1E-06	None	None	None	None	I	None	6.5E-05	0	None	0	0	None	0	None	0	0	0
P/L	rs368758220	0.138	0.003	N	0.307	0.195	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
P/L	rs368758220	0.138	0.003	N	0.307	0.195	None	gnomAD-4.0.0	2.58533E-06	None	None	None	None	I	None	3.41087E-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
P/A	0.0652	likely_benign	0.0707	benign	-0.44	Destabilizing	None	N	0.189	neutral	N	0.511600397	None	None	I
P/C	0.2734	likely_benign	0.3236	benign	-0.5	Destabilizing	0.752	D	0.457	neutral	None	None	None	None	I
P/D	0.2786	likely_benign	0.3011	benign	-0.413	Destabilizing	0.089	N	0.353	neutral	None	None	None	None	I
P/E	0.2139	likely_benign	0.233	benign	-0.528	Destabilizing	0.042	N	0.343	neutral	None	None	None	None	I
P/F	0.2463	likely_benign	0.2741	benign	-0.689	Destabilizing	0.831	D	0.451	neutral	None	None	None	None	I
P/G	0.1967	likely_benign	0.2153	benign	-0.571	Destabilizing	0.124	N	0.33	neutral	None	None	None	None	I
P/H	0.1201	likely_benign	0.1326	benign	-0.173	Destabilizing	0.97	D	0.426	neutral	N	0.476354037	None	None	I
P/I	0.1663	likely_benign	0.1875	benign	-0.244	Destabilizing	0.413	N	0.414	neutral	None	None	None	None	I
P/K	0.1873	likely_benign	0.2045	benign	-0.44	Destabilizing	0.585	D	0.326	neutral	None	None	None	None	I
P/L	0.0892	likely_benign	0.0987	benign	-0.244	Destabilizing	0.003	N	0.307	neutral	N	0.452805278	None	None	I
P/M	0.1925	likely_benign	0.2141	benign	-0.326	Destabilizing	0.649	D	0.416	neutral	None	None	None	None	I
P/N	0.191	likely_benign	0.2102	benign	-0.116	Destabilizing	0.38	N	0.421	neutral	None	None	None	None	I
P/Q	0.1109	likely_benign	0.1217	benign	-0.371	Destabilizing	0.789	D	0.373	neutral	None	None	None	None	I
P/R	0.1217	likely_benign	0.1299	benign	0.085	Stabilizing	0.788	D	0.429	neutral	N	0.457742802	None	None	I
P/S	0.0885	likely_benign	0.1008	benign	-0.436	Destabilizing	0.011	N	0.208	neutral	N	0.462382298	None	None	I
P/T	0.0826	likely_benign	0.0937	benign	-0.455	Destabilizing	0.062	N	0.237	neutral	N	0.510906963	None	None	I
P/V	0.1275	likely_benign	0.1424	benign	-0.275	Destabilizing	0.001	N	0.257	neutral	None	None	None	None	I
P/W	0.3799	ambiguous	0.4241	ambiguous	-0.781	Destabilizing	0.991	D	0.573	neutral	None	None	None	None	I
P/Y	0.2396	likely_benign	0.261	benign	-0.48	Destabilizing	0.909	D	0.458	neutral	None	None	None	None	I

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.