TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9329	28210;28211;28212	chr2:178711251;178711250;178711249	chr2:179575978;179575977;179575976
N2AB	9012	27259;27260;27261	chr2:178711251;178711250;178711249	chr2:179575978;179575977;179575976
N2A	8085	24478;24479;24480	chr2:178711251;178711250;178711249	chr2:179575978;179575977;179575976
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: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-79
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.6138
• Predicted PPI site: I

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	rs1162784959	0.03	0.999	None	0.687	0.426	0.805423805996	gnomAD-2.1.1	4.01E-06	None	None	None	None	I	None	0	0	None	0	5.56E-05	None	0	None	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
P/A	0.178	likely_benign	0.232	benign	-0.389	Destabilizing	0.996	D	0.611	neutral	None	None	None	None	I
P/C	0.7846	likely_pathogenic	0.8577	pathogenic	-0.647	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	I
P/D	0.4662	ambiguous	0.5954	pathogenic	-0.335	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	I
P/E	0.3675	ambiguous	0.4937	ambiguous	-0.453	Destabilizing	0.994	D	0.616	neutral	None	None	None	None	I
P/F	0.6447	likely_pathogenic	0.7603	pathogenic	-0.68	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
P/G	0.4216	ambiguous	0.5409	ambiguous	-0.496	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	I
P/H	0.3674	ambiguous	0.4764	ambiguous	-0.087	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	I
P/I	0.4779	ambiguous	0.6141	pathogenic	-0.259	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
P/K	0.4497	ambiguous	0.5892	pathogenic	-0.42	Destabilizing	0.998	D	0.628	neutral	None	None	None	None	I
P/L	0.2544	likely_benign	0.3333	benign	-0.259	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	I
P/M	0.4665	ambiguous	0.5673	pathogenic	-0.415	Destabilizing	1.0	D	0.66	neutral	None	None	None	None	I
P/N	0.3848	ambiguous	0.498	ambiguous	-0.158	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	I
P/Q	0.3086	likely_benign	0.4087	ambiguous	-0.399	Destabilizing	0.985	D	0.52	neutral	None	None	None	None	I
P/R	0.3387	likely_benign	0.4504	ambiguous	0.083	Stabilizing	0.999	D	0.669	neutral	None	None	None	None	I
P/S	0.2499	likely_benign	0.3402	ambiguous	-0.482	Destabilizing	0.999	D	0.63	neutral	None	None	None	None	I
P/T	0.1921	likely_benign	0.2723	benign	-0.502	Destabilizing	0.999	D	0.639	neutral	None	None	None	None	I
P/V	0.3401	ambiguous	0.4509	ambiguous	-0.27	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	I
P/W	0.8169	likely_pathogenic	0.8965	pathogenic	-0.758	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
P/Y	0.5776	likely_pathogenic	0.6968	pathogenic	-0.461	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I

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.