TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21196	63811;63812;63813	chr2:178587723;178587722;178587721	chr2:179452450;179452449;179452448
N2AB	19555	58888;58889;58890	chr2:178587723;178587722;178587721	chr2:179452450;179452449;179452448
N2A	18628	56107;56108;56109	chr2:178587723;178587722;178587721	chr2:179452450;179452449;179452448
N2B	12131	36616;36617;36618	chr2:178587723;178587722;178587721	chr2:179452450;179452449;179452448
Novex-1	12256	36991;36992;36993	chr2:178587723;178587722;178587721	chr2:179452450;179452449;179452448
Novex-2	12323	37192;37193;37194	chr2:178587723;178587722;178587721	chr2:179452450;179452449;179452448
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-123
• Domain position: 20
• Structural Position: 33
• Q(SASA): 0.162
• 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
A/G	rs1460483373	None	1.0	N	0.708	0.351	0.335164054921	gnomAD-4.0.0	1.59346E-06	None	None	None	None	N	None	0	0	None	0	2.78707E-05	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
A/C	0.6093	likely_pathogenic	0.6285	pathogenic	-0.227	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
A/D	0.9905	likely_pathogenic	0.9907	pathogenic	-1.217	Destabilizing	1.0	D	0.892	deleterious	N	0.487914606	None	None	N
A/E	0.99	likely_pathogenic	0.9898	pathogenic	-1.065	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
A/F	0.956	likely_pathogenic	0.9579	pathogenic	-0.558	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
A/G	0.1514	likely_benign	0.2469	benign	-1.029	Destabilizing	1.0	D	0.708	prob.delet.	N	0.491977273	None	None	N
A/H	0.9895	likely_pathogenic	0.9898	pathogenic	-1.194	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
A/I	0.8416	likely_pathogenic	0.8229	pathogenic	0.378	Stabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
A/K	0.9956	likely_pathogenic	0.996	pathogenic	-0.517	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
A/L	0.7483	likely_pathogenic	0.7532	pathogenic	0.378	Stabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
A/M	0.857	likely_pathogenic	0.8555	pathogenic	0.288	Stabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
A/N	0.9709	likely_pathogenic	0.9722	pathogenic	-0.665	Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
A/P	0.9621	likely_pathogenic	0.9609	pathogenic	0.081	Stabilizing	1.0	D	0.877	deleterious	N	0.487914606	None	None	N
A/Q	0.9763	likely_pathogenic	0.9778	pathogenic	-0.558	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
A/R	0.9868	likely_pathogenic	0.9875	pathogenic	-0.587	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
A/S	0.2512	likely_benign	0.2576	benign	-1.078	Destabilizing	1.0	D	0.707	prob.neutral	N	0.457782482	None	None	N
A/T	0.4325	ambiguous	0.4181	ambiguous	-0.799	Destabilizing	1.0	D	0.85	deleterious	N	0.457693577	None	None	N
A/V	0.5483	ambiguous	0.4984	ambiguous	0.081	Stabilizing	1.0	D	0.768	deleterious	N	0.380497207	None	None	N
A/W	0.9951	likely_pathogenic	0.9956	pathogenic	-1.163	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
A/Y	0.9828	likely_pathogenic	0.9829	pathogenic	-0.536	Destabilizing	1.0	D	0.912	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.