TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5753	17482;17483;17484	chr2:178731509;178731508;178731507	chr2:179596236;179596235;179596234
N2AB	5436	16531;16532;16533	chr2:178731509;178731508;178731507	chr2:179596236;179596235;179596234
N2A	4509	13750;13751;13752	chr2:178731509;178731508;178731507	chr2:179596236;179596235;179596234
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: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-41
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.0907
• 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
L/Q	None	None	0.995	D	0.806	0.566	0.82834384376	gnomAD-4.0.0	6.84338E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99543E-07	0	0
L/R	None	None	0.984	D	0.813	0.628	0.813981597967	gnomAD-4.0.0	6.84338E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99543E-07	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
L/A	0.7989	likely_pathogenic	0.8053	pathogenic	-2.549	Highly Destabilizing	0.851	D	0.711	prob.delet.	None	None	None	None	N
L/C	0.8226	likely_pathogenic	0.8083	pathogenic	-1.687	Destabilizing	0.999	D	0.762	deleterious	None	None	None	None	N
L/D	0.9979	likely_pathogenic	0.9975	pathogenic	-2.696	Highly Destabilizing	0.996	D	0.843	deleterious	None	None	None	None	N
L/E	0.9811	likely_pathogenic	0.9798	pathogenic	-2.421	Highly Destabilizing	0.988	D	0.843	deleterious	None	None	None	None	N
L/F	0.4874	ambiguous	0.4106	ambiguous	-1.474	Destabilizing	0.976	D	0.759	deleterious	None	None	None	None	N
L/G	0.9716	likely_pathogenic	0.9706	pathogenic	-3.14	Highly Destabilizing	0.988	D	0.841	deleterious	None	None	None	None	N
L/H	0.9674	likely_pathogenic	0.9597	pathogenic	-2.631	Highly Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
L/I	0.0899	likely_benign	0.0843	benign	-0.814	Destabilizing	0.034	N	0.299	neutral	None	None	None	None	N
L/K	0.9812	likely_pathogenic	0.9785	pathogenic	-1.753	Destabilizing	0.988	D	0.824	deleterious	None	None	None	None	N
L/M	0.2016	likely_benign	0.192	benign	-0.818	Destabilizing	0.968	D	0.733	prob.delet.	D	0.535771775	None	None	N
L/N	0.9858	likely_pathogenic	0.9836	pathogenic	-2.208	Highly Destabilizing	0.996	D	0.831	deleterious	None	None	None	None	N
L/P	0.9804	likely_pathogenic	0.9784	pathogenic	-1.377	Destabilizing	0.995	D	0.844	deleterious	N	0.483862875	None	None	N
L/Q	0.9396	likely_pathogenic	0.9382	pathogenic	-1.971	Destabilizing	0.995	D	0.806	deleterious	D	0.536118492	None	None	N
L/R	0.9616	likely_pathogenic	0.9587	pathogenic	-1.654	Destabilizing	0.984	D	0.813	deleterious	D	0.536118492	None	None	N
L/S	0.9544	likely_pathogenic	0.9515	pathogenic	-2.938	Highly Destabilizing	0.988	D	0.812	deleterious	None	None	None	None	N
L/T	0.8085	likely_pathogenic	0.8041	pathogenic	-2.505	Highly Destabilizing	0.919	D	0.759	deleterious	None	None	None	None	N
L/V	0.0795	likely_benign	0.0787	benign	-1.377	Destabilizing	0.011	N	0.283	neutral	N	0.367312558	None	None	N
L/W	0.91	likely_pathogenic	0.8824	pathogenic	-1.862	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
L/Y	0.9337	likely_pathogenic	0.9061	pathogenic	-1.578	Destabilizing	0.996	D	0.789	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.