TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29957	90094;90095;90096	chr2:178553031;178553030;178553029	chr2:179417758;179417757;179417756
N2AB	28316	85171;85172;85173	chr2:178553031;178553030;178553029	chr2:179417758;179417757;179417756
N2A	27389	82390;82391;82392	chr2:178553031;178553030;178553029	chr2:179417758;179417757;179417756
N2B	20892	62899;62900;62901	chr2:178553031;178553030;178553029	chr2:179417758;179417757;179417756
Novex-1	21017	63274;63275;63276	chr2:178553031;178553030;178553029	chr2:179417758;179417757;179417756
Novex-2	21084	63475;63476;63477	chr2:178553031;178553030;178553029	chr2:179417758;179417757;179417756
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: Fn3-106
• Domain position: 25
• Structural Position: 27
• Q(SASA): 0.1625
• 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
P/T	rs1164517962	-2.12	0.978	D	0.811	0.642	0.631129199617	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
P/T	rs1164517962	-2.12	0.978	D	0.811	0.642	0.631129199617	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/T	rs1164517962	-2.12	0.978	D	0.811	0.642	0.631129199617	gnomAD-4.0.0	1.92349E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62765E-05	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	0.884	likely_pathogenic	0.8711	pathogenic	-1.963	Destabilizing	0.928	D	0.705	prob.neutral	D	0.600866693	None	None	N
P/C	0.9892	likely_pathogenic	0.9866	pathogenic	-1.251	Destabilizing	0.999	D	0.871	deleterious	None	None	None	None	N
P/D	0.999	likely_pathogenic	0.9992	pathogenic	-2.552	Highly Destabilizing	0.983	D	0.824	deleterious	None	None	None	None	N
P/E	0.9978	likely_pathogenic	0.9981	pathogenic	-2.487	Highly Destabilizing	0.983	D	0.813	deleterious	None	None	None	None	N
P/F	0.9995	likely_pathogenic	0.9995	pathogenic	-1.418	Destabilizing	0.999	D	0.892	deleterious	None	None	None	None	N
P/G	0.9913	likely_pathogenic	0.9928	pathogenic	-2.353	Highly Destabilizing	0.983	D	0.858	deleterious	None	None	None	None	N
P/H	0.9968	likely_pathogenic	0.9971	pathogenic	-2.129	Highly Destabilizing	0.997	D	0.885	deleterious	D	0.652548329	None	None	N
P/I	0.9939	likely_pathogenic	0.9935	pathogenic	-0.936	Destabilizing	0.992	D	0.885	deleterious	None	None	None	None	N
P/K	0.9988	likely_pathogenic	0.999	pathogenic	-1.793	Destabilizing	0.895	D	0.756	deleterious	None	None	None	None	N
P/L	0.9753	likely_pathogenic	0.9738	pathogenic	-0.936	Destabilizing	0.978	D	0.882	deleterious	D	0.651539308	None	None	N
P/M	0.9969	likely_pathogenic	0.9968	pathogenic	-0.641	Destabilizing	0.999	D	0.881	deleterious	None	None	None	None	N
P/N	0.9983	likely_pathogenic	0.9986	pathogenic	-1.682	Destabilizing	0.983	D	0.888	deleterious	None	None	None	None	N
P/Q	0.9959	likely_pathogenic	0.9961	pathogenic	-1.777	Destabilizing	0.983	D	0.826	deleterious	None	None	None	None	N
P/R	0.9957	likely_pathogenic	0.9962	pathogenic	-1.312	Destabilizing	0.085	N	0.633	neutral	D	0.636094999	None	None	N
P/S	0.9744	likely_pathogenic	0.9747	pathogenic	-2.125	Highly Destabilizing	0.978	D	0.817	deleterious	D	0.588622687	None	None	N
P/T	0.98	likely_pathogenic	0.9802	pathogenic	-1.96	Destabilizing	0.978	D	0.811	deleterious	D	0.626606609	None	None	N
P/V	0.9752	likely_pathogenic	0.9737	pathogenic	-1.249	Destabilizing	0.992	D	0.883	deleterious	None	None	None	None	N
P/W	0.9999	likely_pathogenic	0.9999	pathogenic	-1.82	Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	N
P/Y	0.9994	likely_pathogenic	0.9995	pathogenic	-1.531	Destabilizing	0.999	D	0.891	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.