TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23025	69298;69299;69300	chr2:178577262;178577261;178577260	chr2:179441989;179441988;179441987
N2AB	21384	64375;64376;64377	chr2:178577262;178577261;178577260	chr2:179441989;179441988;179441987
N2A	20457	61594;61595;61596	chr2:178577262;178577261;178577260	chr2:179441989;179441988;179441987
N2B	13960	42103;42104;42105	chr2:178577262;178577261;178577260	chr2:179441989;179441988;179441987
Novex-1	14085	42478;42479;42480	chr2:178577262;178577261;178577260	chr2:179441989;179441988;179441987
Novex-2	14152	42679;42680;42681	chr2:178577262;178577261;178577260	chr2:179441989;179441988;179441987
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-128
• Domain position: 76
• Structural Position: 162
• Q(SASA): 0.6982
• 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/A	None	None	0.016	N	0.39	0.19	0.185906805712	gnomAD-4.0.0	6.84462E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.15974E-05	0
P/L	None	None	0.898	N	0.594	0.399	0.5073929853	gnomAD-4.0.0	1.59262E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85997E-06	0	0
P/S	None	None	0.898	N	0.517	0.247	0.24896430686	gnomAD-4.0.0	6.84462E-07	None	None	None	None	I	None	0	0	None	0	2.53036E-05	None	0	0	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	0.143	likely_benign	0.1359	benign	-0.507	Destabilizing	0.016	N	0.39	neutral	N	0.470469503	None	None	I
P/C	0.6865	likely_pathogenic	0.687	pathogenic	-0.735	Destabilizing	0.994	D	0.707	prob.neutral	None	None	None	None	I
P/D	0.7095	likely_pathogenic	0.7257	pathogenic	-0.243	Destabilizing	0.959	D	0.57	neutral	None	None	None	None	I
P/E	0.5581	ambiguous	0.5793	pathogenic	-0.331	Destabilizing	0.959	D	0.567	neutral	None	None	None	None	I
P/F	0.8236	likely_pathogenic	0.7822	pathogenic	-0.678	Destabilizing	0.994	D	0.68	prob.neutral	None	None	None	None	I
P/G	0.5493	ambiguous	0.5802	pathogenic	-0.639	Destabilizing	0.769	D	0.493	neutral	None	None	None	None	I
P/H	0.4625	ambiguous	0.4415	ambiguous	-0.097	Destabilizing	0.998	D	0.657	neutral	N	0.486124083	None	None	I
P/I	0.4568	ambiguous	0.3931	ambiguous	-0.298	Destabilizing	0.959	D	0.672	neutral	None	None	None	None	I
P/K	0.6499	likely_pathogenic	0.6566	pathogenic	-0.431	Destabilizing	0.959	D	0.572	neutral	None	None	None	None	I
P/L	0.2663	likely_benign	0.2411	benign	-0.298	Destabilizing	0.898	D	0.594	neutral	N	0.512105482	None	None	I
P/M	0.5232	ambiguous	0.4797	ambiguous	-0.537	Destabilizing	0.994	D	0.653	neutral	None	None	None	None	I
P/N	0.5402	ambiguous	0.5424	ambiguous	-0.254	Destabilizing	0.979	D	0.64	neutral	None	None	None	None	I
P/Q	0.4063	ambiguous	0.404	ambiguous	-0.436	Destabilizing	0.979	D	0.587	neutral	None	None	None	None	I
P/R	0.4835	ambiguous	0.4819	ambiguous	0.043	Stabilizing	0.946	D	0.64	neutral	N	0.507545024	None	None	I
P/S	0.2335	likely_benign	0.2639	benign	-0.625	Destabilizing	0.898	D	0.517	neutral	N	0.474525742	None	None	I
P/T	0.1861	likely_benign	0.1835	benign	-0.606	Destabilizing	0.898	D	0.537	neutral	N	0.486169674	None	None	I
P/V	0.3311	likely_benign	0.2873	benign	-0.335	Destabilizing	0.921	D	0.525	neutral	None	None	None	None	I
P/W	0.9111	likely_pathogenic	0.8991	pathogenic	-0.754	Destabilizing	0.998	D	0.747	deleterious	None	None	None	None	I
P/Y	0.736	likely_pathogenic	0.7123	pathogenic	-0.466	Destabilizing	0.998	D	0.681	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.