TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9139	27640;27641;27642	chr2:178712507;178712506;178712505	chr2:179577234;179577233;179577232
N2AB	8822	26689;26690;26691	chr2:178712507;178712506;178712505	chr2:179577234;179577233;179577232
N2A	7895	23908;23909;23910	chr2:178712507;178712506;178712505	chr2:179577234;179577233;179577232
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-77
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.5251
• 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	rs770133378	0.035	0.018	D	0.327	0.478	0.585352569408	gnomAD-2.1.1	8.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
P/L	rs770133378	0.035	0.018	D	0.327	0.478	0.585352569408	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	4.14422E-04	0
P/L	rs770133378	0.035	0.018	D	0.327	0.478	0.585352569408	gnomAD-4.0.0	1.36338E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.41546E-04	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	0.1648	likely_benign	0.0879	benign	-0.319	Destabilizing	0.349	N	0.437	neutral	N	0.521791113	None	None	I
P/C	0.6874	likely_pathogenic	0.5422	ambiguous	-0.581	Destabilizing	0.996	D	0.623	neutral	None	None	None	None	I
P/D	0.6402	likely_pathogenic	0.4374	ambiguous	-0.485	Destabilizing	0.923	D	0.441	neutral	None	None	None	None	I
P/E	0.3713	ambiguous	0.2441	benign	-0.605	Destabilizing	0.923	D	0.435	neutral	None	None	None	None	I
P/F	0.5282	ambiguous	0.3588	ambiguous	-0.677	Destabilizing	0.858	D	0.616	neutral	None	None	None	None	I
P/G	0.5776	likely_pathogenic	0.3819	ambiguous	-0.408	Destabilizing	0.011	N	0.262	neutral	None	None	None	None	I
P/H	0.3257	likely_benign	0.1822	benign	-0.062	Destabilizing	0.986	D	0.518	neutral	D	0.597152058	None	None	I
P/I	0.2909	likely_benign	0.2224	benign	-0.231	Destabilizing	0.858	D	0.594	neutral	None	None	None	None	I
P/K	0.4849	ambiguous	0.2939	benign	-0.418	Destabilizing	0.858	D	0.438	neutral	None	None	None	None	I
P/L	0.111	likely_benign	0.0762	benign	-0.231	Destabilizing	0.018	N	0.327	neutral	D	0.540968213	None	None	I
P/M	0.3138	likely_benign	0.2141	benign	-0.446	Destabilizing	0.979	D	0.525	neutral	None	None	None	None	I
P/N	0.5373	ambiguous	0.3307	benign	-0.128	Destabilizing	0.858	D	0.502	neutral	None	None	None	None	I
P/Q	0.2554	likely_benign	0.1314	benign	-0.373	Destabilizing	0.923	D	0.431	neutral	None	None	None	None	I
P/R	0.3582	ambiguous	0.201	benign	0.063	Stabilizing	0.901	D	0.519	neutral	D	0.603481225	None	None	I
P/S	0.265	likely_benign	0.1212	benign	-0.392	Destabilizing	0.075	N	0.254	neutral	D	0.534944617	None	None	I
P/T	0.1932	likely_benign	0.1117	benign	-0.423	Destabilizing	0.565	D	0.453	neutral	D	0.583747229	None	None	I
P/V	0.2304	likely_benign	0.165	benign	-0.229	Destabilizing	0.633	D	0.472	neutral	None	None	None	None	I
P/W	0.7341	likely_pathogenic	0.5894	pathogenic	-0.768	Destabilizing	0.996	D	0.647	neutral	None	None	None	None	I
P/Y	0.5213	ambiguous	0.3563	ambiguous	-0.47	Destabilizing	0.961	D	0.616	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.