TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15552	46879;46880;46881	chr2:178619663;178619662;178619661	chr2:179484390;179484389;179484388
N2AB	13911	41956;41957;41958	chr2:178619663;178619662;178619661	chr2:179484390;179484389;179484388
N2A	12984	39175;39176;39177	chr2:178619663;178619662;178619661	chr2:179484390;179484389;179484388
N2B	6487	19684;19685;19686	chr2:178619663;178619662;178619661	chr2:179484390;179484389;179484388
Novex-1	6612	20059;20060;20061	chr2:178619663;178619662;178619661	chr2:179484390;179484389;179484388
Novex-2	6679	20260;20261;20262	chr2:178619663;178619662;178619661	chr2:179484390;179484389;179484388
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-107
• Domain position: 73
• Structural Position: 157
• Q(SASA): 0.1258
• 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
I/T	rs1292128337	-2.11	0.822	N	0.678	0.285	0.675543170505	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
I/T	rs1292128337	-2.11	0.822	N	0.678	0.285	0.675543170505	gnomAD-4.0.0	3.18972E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.42365E-04	2.86513E-06	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
I/A	0.435	ambiguous	0.4327	ambiguous	-2.295	Highly Destabilizing	0.754	D	0.681	prob.neutral	None	None	None	None	N
I/C	0.7744	likely_pathogenic	0.7508	pathogenic	-1.494	Destabilizing	0.994	D	0.711	prob.delet.	None	None	None	None	N
I/D	0.9387	likely_pathogenic	0.9249	pathogenic	-2.358	Highly Destabilizing	0.993	D	0.813	deleterious	None	None	None	None	N
I/E	0.7706	likely_pathogenic	0.729	pathogenic	-2.166	Highly Destabilizing	0.978	D	0.805	deleterious	None	None	None	None	N
I/F	0.2431	likely_benign	0.2453	benign	-1.29	Destabilizing	0.942	D	0.665	neutral	N	0.510809462	None	None	N
I/G	0.8698	likely_pathogenic	0.8476	pathogenic	-2.809	Highly Destabilizing	0.978	D	0.797	deleterious	None	None	None	None	N
I/H	0.6245	likely_pathogenic	0.6009	pathogenic	-2.226	Highly Destabilizing	0.998	D	0.797	deleterious	None	None	None	None	N
I/K	0.3815	ambiguous	0.3808	ambiguous	-1.674	Destabilizing	0.978	D	0.801	deleterious	None	None	None	None	N
I/L	0.1564	likely_benign	0.1593	benign	-0.832	Destabilizing	0.294	N	0.423	neutral	N	0.496345655	None	None	N
I/M	0.1431	likely_benign	0.1468	benign	-0.774	Destabilizing	0.942	D	0.661	neutral	N	0.510809462	None	None	N
I/N	0.6222	likely_pathogenic	0.6014	pathogenic	-1.882	Destabilizing	0.99	D	0.82	deleterious	N	0.508416315	None	None	N
I/P	0.982	likely_pathogenic	0.9825	pathogenic	-1.298	Destabilizing	0.993	D	0.817	deleterious	None	None	None	None	N
I/Q	0.51	ambiguous	0.4612	ambiguous	-1.793	Destabilizing	0.993	D	0.815	deleterious	None	None	None	None	N
I/R	0.2992	likely_benign	0.296	benign	-1.364	Destabilizing	0.978	D	0.82	deleterious	None	None	None	None	N
I/S	0.4599	ambiguous	0.4463	ambiguous	-2.586	Highly Destabilizing	0.942	D	0.754	deleterious	N	0.506197063	None	None	N
I/T	0.2084	likely_benign	0.2303	benign	-2.258	Highly Destabilizing	0.822	D	0.678	prob.neutral	N	0.493388236	None	None	N
I/V	0.0824	likely_benign	0.0882	benign	-1.298	Destabilizing	0.006	N	0.299	neutral	N	0.431149027	None	None	N
I/W	0.8305	likely_pathogenic	0.8286	pathogenic	-1.656	Destabilizing	0.998	D	0.755	deleterious	None	None	None	None	N
I/Y	0.6776	likely_pathogenic	0.6431	pathogenic	-1.36	Destabilizing	0.978	D	0.73	prob.delet.	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.