TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31688	95287;95288;95289	chr2:178546269;178546268;178546267	chr2:179410996;179410995;179410994
N2AB	30047	90364;90365;90366	chr2:178546269;178546268;178546267	chr2:179410996;179410995;179410994
N2A	29120	87583;87584;87585	chr2:178546269;178546268;178546267	chr2:179410996;179410995;179410994
N2B	22623	68092;68093;68094	chr2:178546269;178546268;178546267	chr2:179410996;179410995;179410994
Novex-1	22748	68467;68468;68469	chr2:178546269;178546268;178546267	chr2:179410996;179410995;179410994
Novex-2	22815	68668;68669;68670	chr2:178546269;178546268;178546267	chr2:179410996;179410995;179410994
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-152
• Domain position: 68
• Structural Position: 156
• Q(SASA): 0.0955
• 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/S	rs794729538	None	1.0	N	0.864	0.552	0.767629022357	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
L/A	0.9396	likely_pathogenic	0.9439	pathogenic	-2.09	Highly Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
L/C	0.9118	likely_pathogenic	0.9126	pathogenic	-1.434	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
L/D	0.9999	likely_pathogenic	0.9999	pathogenic	-1.853	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
L/E	0.9988	likely_pathogenic	0.9987	pathogenic	-1.705	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
L/F	0.8557	likely_pathogenic	0.8451	pathogenic	-1.278	Destabilizing	1.0	D	0.832	deleterious	N	0.459819944	None	None	N
L/G	0.9955	likely_pathogenic	0.9955	pathogenic	-2.571	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
L/H	0.9976	likely_pathogenic	0.9975	pathogenic	-1.911	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
L/I	0.1628	likely_benign	0.1606	benign	-0.754	Destabilizing	0.999	D	0.699	prob.neutral	N	0.488454178	None	None	N
L/K	0.9975	likely_pathogenic	0.9971	pathogenic	-1.451	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
L/M	0.4215	ambiguous	0.4235	ambiguous	-0.685	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
L/N	0.9989	likely_pathogenic	0.9988	pathogenic	-1.58	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
L/P	0.9987	likely_pathogenic	0.9984	pathogenic	-1.174	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
L/Q	0.9941	likely_pathogenic	0.9936	pathogenic	-1.555	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
L/R	0.9943	likely_pathogenic	0.9935	pathogenic	-1.086	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
L/S	0.9971	likely_pathogenic	0.9971	pathogenic	-2.316	Highly Destabilizing	1.0	D	0.864	deleterious	N	0.502157747	None	None	N
L/T	0.9844	likely_pathogenic	0.9846	pathogenic	-2.025	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
L/V	0.1686	likely_benign	0.1684	benign	-1.174	Destabilizing	0.999	D	0.725	prob.delet.	N	0.491801128	None	None	N
L/W	0.9944	likely_pathogenic	0.9935	pathogenic	-1.549	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
L/Y	0.9929	likely_pathogenic	0.992	pathogenic	-1.244	Destabilizing	1.0	D	0.838	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.