TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8484	25675;25676;25677	chr2:178717284;178717283;178717282	chr2:179582011;179582010;179582009
N2AB	8167	24724;24725;24726	chr2:178717284;178717283;178717282	chr2:179582011;179582010;179582009
N2A	7240	21943;21944;21945	chr2:178717284;178717283;178717282	chr2:179582011;179582010;179582009
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: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-70
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.7256
• 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/Q	None	None	1.0	N	0.65	0.42	0.585534595853	gnomAD-4.0.0	4.77487E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	4.82393E-04	0	0	3.02499E-05

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	0.252	likely_benign	0.1646	benign	-0.356	Destabilizing	0.497	N	0.451	neutral	N	0.489629576	None	None	I
P/C	0.94	likely_pathogenic	0.8763	pathogenic	-0.623	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	I
P/D	0.7387	likely_pathogenic	0.6217	pathogenic	-0.314	Destabilizing	0.994	D	0.665	neutral	None	None	None	None	I
P/E	0.6391	likely_pathogenic	0.5038	ambiguous	-0.43	Destabilizing	0.996	D	0.665	neutral	None	None	None	None	I
P/F	0.9109	likely_pathogenic	0.8192	pathogenic	-0.651	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	I
P/G	0.666	likely_pathogenic	0.5322	ambiguous	-0.463	Destabilizing	0.996	D	0.643	neutral	None	None	None	None	I
P/H	0.6324	likely_pathogenic	0.4623	ambiguous	-0.076	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	I
P/I	0.78	likely_pathogenic	0.6397	pathogenic	-0.224	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	I
P/K	0.7182	likely_pathogenic	0.5751	pathogenic	-0.4	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	I
P/L	0.4417	ambiguous	0.3094	benign	-0.224	Destabilizing	1.0	D	0.656	neutral	N	0.499366493	None	None	I
P/M	0.7578	likely_pathogenic	0.6294	pathogenic	-0.398	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	I
P/N	0.6493	likely_pathogenic	0.5155	ambiguous	-0.138	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	I
P/Q	0.4959	ambiguous	0.3472	ambiguous	-0.368	Destabilizing	1.0	D	0.65	neutral	N	0.48218361	None	None	I
P/R	0.5503	ambiguous	0.4025	ambiguous	0.082	Stabilizing	1.0	D	0.669	neutral	N	0.487845604	None	None	I
P/S	0.4062	ambiguous	0.2782	benign	-0.457	Destabilizing	0.998	D	0.654	neutral	N	0.500910202	None	None	I
P/T	0.3835	ambiguous	0.2611	benign	-0.475	Destabilizing	0.997	D	0.641	neutral	N	0.480475316	None	None	I
P/V	0.6057	likely_pathogenic	0.453	ambiguous	-0.235	Destabilizing	0.999	D	0.637	neutral	None	None	None	None	I
P/W	0.962	likely_pathogenic	0.9194	pathogenic	-0.738	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
P/Y	0.8905	likely_pathogenic	0.7925	pathogenic	-0.437	Destabilizing	1.0	D	0.657	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.