TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15307	46144;46145;46146	chr2:178620602;178620601;178620600	chr2:179485329;179485328;179485327
N2AB	13666	41221;41222;41223	chr2:178620602;178620601;178620600	chr2:179485329;179485328;179485327
N2A	12739	38440;38441;38442	chr2:178620602;178620601;178620600	chr2:179485329;179485328;179485327
N2B	6242	18949;18950;18951	chr2:178620602;178620601;178620600	chr2:179485329;179485328;179485327
Novex-1	6367	19324;19325;19326	chr2:178620602;178620601;178620600	chr2:179485329;179485328;179485327
Novex-2	6434	19525;19526;19527	chr2:178620602;178620601;178620600	chr2:179485329;179485328;179485327
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-105
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.5574
• 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
P/L	rs749054832	-0.331	1.0	D	0.82	0.496	0.697412557007	gnomAD-2.1.1	4.09E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.01E-06	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
P/A	0.1888	likely_benign	0.1704	benign	-1.146	Destabilizing	1.0	D	0.772	deleterious	D	0.564340692	None	None	N
P/C	0.795	likely_pathogenic	0.788	pathogenic	-0.713	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
P/D	0.6218	likely_pathogenic	0.5852	pathogenic	-0.746	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
P/E	0.476	ambiguous	0.4502	ambiguous	-0.75	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
P/F	0.8166	likely_pathogenic	0.7732	pathogenic	-0.808	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
P/G	0.5396	ambiguous	0.5339	ambiguous	-1.449	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
P/H	0.4409	ambiguous	0.3509	ambiguous	-0.967	Destabilizing	1.0	D	0.738	prob.delet.	N	0.509106312	None	None	N
P/I	0.6429	likely_pathogenic	0.5975	pathogenic	-0.429	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
P/K	0.501	ambiguous	0.4388	ambiguous	-0.942	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
P/L	0.32	likely_benign	0.267	benign	-0.429	Destabilizing	1.0	D	0.82	deleterious	D	0.552342356	None	None	N
P/M	0.6105	likely_pathogenic	0.5887	pathogenic	-0.362	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
P/N	0.5435	ambiguous	0.5075	ambiguous	-0.716	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
P/Q	0.3434	ambiguous	0.2909	benign	-0.858	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
P/R	0.4032	ambiguous	0.3178	benign	-0.475	Destabilizing	1.0	D	0.795	deleterious	D	0.541720874	None	None	N
P/S	0.2856	likely_benign	0.2499	benign	-1.238	Destabilizing	1.0	D	0.831	deleterious	D	0.582822414	None	None	N
P/T	0.2548	likely_benign	0.2181	benign	-1.13	Destabilizing	1.0	D	0.829	deleterious	D	0.607042064	None	None	N
P/V	0.4801	ambiguous	0.4483	ambiguous	-0.632	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
P/W	0.9064	likely_pathogenic	0.869	pathogenic	-0.995	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
P/Y	0.7281	likely_pathogenic	0.6687	pathogenic	-0.692	Destabilizing	1.0	D	0.757	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.