TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1515	4768;4769;4770	chr2:178777522;178777521;178777520	chr2:179642249;179642248;179642247
N2AB	1515	4768;4769;4770	chr2:178777522;178777521;178777520	chr2:179642249;179642248;179642247
N2A	1515	4768;4769;4770	chr2:178777522;178777521;178777520	chr2:179642249;179642248;179642247
N2B	1469	4630;4631;4632	chr2:178777522;178777521;178777520	chr2:179642249;179642248;179642247
Novex-1	1469	4630;4631;4632	chr2:178777522;178777521;178777520	chr2:179642249;179642248;179642247
Novex-2	1469	4630;4631;4632	chr2:178777522;178777521;178777520	chr2:179642249;179642248;179642247
Novex-3	1515	4768;4769;4770	chr2:178777522;178777521;178777520	chr2:179642249;179642248;179642247

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-6
• Domain position: 59
• Structural Position: 138
• Q(SASA): 0.0952
• 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/V	None	None	0.984	D	0.673	0.547	0.859270295341	gnomAD-4.0.0	6.8419E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9936E-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	0.9623	likely_pathogenic	0.9595	pathogenic	-2.256	Highly Destabilizing	0.994	D	0.757	deleterious	None	None	None	None	N
L/C	0.928	likely_pathogenic	0.9233	pathogenic	-1.53	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/D	0.9998	likely_pathogenic	0.9998	pathogenic	-3.016	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
L/E	0.9981	likely_pathogenic	0.998	pathogenic	-2.686	Highly Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
L/F	0.553	ambiguous	0.565	pathogenic	-1.4	Destabilizing	0.998	D	0.781	deleterious	None	None	None	None	N
L/G	0.9957	likely_pathogenic	0.9955	pathogenic	-2.857	Highly Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	N
L/H	0.9897	likely_pathogenic	0.9888	pathogenic	-2.841	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
L/I	0.3711	ambiguous	0.3602	ambiguous	-0.44	Destabilizing	0.984	D	0.657	neutral	D	0.692160077	None	None	N
L/K	0.9951	likely_pathogenic	0.9949	pathogenic	-1.688	Destabilizing	0.999	D	0.886	deleterious	None	None	None	None	N
L/M	0.2445	likely_benign	0.2478	benign	-0.71	Destabilizing	0.971	D	0.605	neutral	None	None	None	None	N
L/N	0.9977	likely_pathogenic	0.9975	pathogenic	-2.459	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/P	0.9994	likely_pathogenic	0.9994	pathogenic	-1.037	Destabilizing	1.0	D	0.905	deleterious	D	0.78148854	None	None	N
L/Q	0.9828	likely_pathogenic	0.9821	pathogenic	-2.016	Highly Destabilizing	0.999	D	0.901	deleterious	D	0.78148854	None	None	N
L/R	0.9875	likely_pathogenic	0.9876	pathogenic	-2.035	Highly Destabilizing	0.999	D	0.885	deleterious	D	0.78148854	None	None	N
L/S	0.9955	likely_pathogenic	0.9947	pathogenic	-2.933	Highly Destabilizing	0.999	D	0.882	deleterious	None	None	None	None	N
L/T	0.9849	likely_pathogenic	0.9829	pathogenic	-2.426	Highly Destabilizing	0.999	D	0.822	deleterious	None	None	None	None	N
L/V	0.3643	ambiguous	0.3757	ambiguous	-1.037	Destabilizing	0.984	D	0.673	neutral	D	0.69022908	None	None	N
L/W	0.9638	likely_pathogenic	0.9645	pathogenic	-1.782	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
L/Y	0.9704	likely_pathogenic	0.9698	pathogenic	-1.549	Destabilizing	1.0	D	0.849	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.