TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1372	4339;4340;4341	chr2:178778968;178778967;178778966	chr2:179643695;179643694;179643693
N2AB	1372	4339;4340;4341	chr2:178778968;178778967;178778966	chr2:179643695;179643694;179643693
N2A	1372	4339;4340;4341	chr2:178778968;178778967;178778966	chr2:179643695;179643694;179643693
N2B	1326	4201;4202;4203	chr2:178778968;178778967;178778966	chr2:179643695;179643694;179643693
Novex-1	1326	4201;4202;4203	chr2:178778968;178778967;178778966	chr2:179643695;179643694;179643693
Novex-2	1326	4201;4202;4203	chr2:178778968;178778967;178778966	chr2:179643695;179643694;179643693
Novex-3	1372	4339;4340;4341	chr2:178778968;178778967;178778966	chr2:179643695;179643694;179643693

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-5
• Domain position: 82
• Structural Position: 165
• Q(SASA): 0.6131
• 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
N/H	rs745676502	-0.863	1.0	N	0.713	0.433	0.352048277211	gnomAD-2.1.1	3.99E-06	None	None	None	None	I	None	6.15E-05	0	None	0	0	None	0	None	0	0	0
N/H	rs745676502	-0.863	1.0	N	0.713	0.433	0.352048277211	gnomAD-4.0.0	3.18168E-06	None	None	None	None	I	None	5.65675E-05	0	None	0	0	None	0	0	0	0	3.02224E-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
N/A	0.8163	likely_pathogenic	0.8212	pathogenic	-0.75	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	I
N/C	0.805	likely_pathogenic	0.795	pathogenic	0.154	Stabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	I
N/D	0.7166	likely_pathogenic	0.6978	pathogenic	0.106	Stabilizing	0.999	D	0.699	prob.neutral	N	0.47686953	None	None	I
N/E	0.9101	likely_pathogenic	0.9173	pathogenic	0.088	Stabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	I
N/F	0.9268	likely_pathogenic	0.9306	pathogenic	-1.102	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
N/G	0.8748	likely_pathogenic	0.868	pathogenic	-0.933	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	I
N/H	0.4138	ambiguous	0.4276	ambiguous	-0.922	Destabilizing	1.0	D	0.713	prob.delet.	N	0.48790916	None	None	I
N/I	0.7822	likely_pathogenic	0.7966	pathogenic	-0.345	Destabilizing	1.0	D	0.711	prob.delet.	N	0.47101159	None	None	I
N/K	0.8979	likely_pathogenic	0.9075	pathogenic	0.058	Stabilizing	1.0	D	0.735	prob.delet.	N	0.404570413	None	None	I
N/L	0.7944	likely_pathogenic	0.7984	pathogenic	-0.345	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
N/M	0.8285	likely_pathogenic	0.834	pathogenic	0.192	Stabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	I
N/P	0.9769	likely_pathogenic	0.9671	pathogenic	-0.455	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
N/Q	0.8329	likely_pathogenic	0.8516	pathogenic	-0.505	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
N/R	0.8672	likely_pathogenic	0.8769	pathogenic	0.143	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
N/S	0.304	likely_benign	0.2878	benign	-0.338	Destabilizing	0.999	D	0.653	neutral	N	0.373988956	None	None	I
N/T	0.5746	likely_pathogenic	0.5666	pathogenic	-0.192	Destabilizing	0.999	D	0.739	prob.delet.	N	0.42855128	None	None	I
N/V	0.7587	likely_pathogenic	0.7709	pathogenic	-0.455	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	I
N/W	0.981	likely_pathogenic	0.9804	pathogenic	-0.977	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	I
N/Y	0.5718	likely_pathogenic	0.584	pathogenic	-0.75	Destabilizing	1.0	D	0.693	prob.neutral	N	0.485336317	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.