TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22277	67054;67055;67056	chr2:178580550;178580549;178580548	chr2:179445277;179445276;179445275
N2AB	20636	62131;62132;62133	chr2:178580550;178580549;178580548	chr2:179445277;179445276;179445275
N2A	19709	59350;59351;59352	chr2:178580550;178580549;178580548	chr2:179445277;179445276;179445275
N2B	13212	39859;39860;39861	chr2:178580550;178580549;178580548	chr2:179445277;179445276;179445275
Novex-1	13337	40234;40235;40236	chr2:178580550;178580549;178580548	chr2:179445277;179445276;179445275
Novex-2	13404	40435;40436;40437	chr2:178580550;178580549;178580548	chr2:179445277;179445276;179445275
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-126
• Domain position: 13
• Structural Position: 25
• Q(SASA): 0.2327
• 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
V/A	rs768860754	-1.226	0.63	N	0.454	0.134	0.367992661779	gnomAD-2.1.1	4.05E-06	None	None	None	None	I	None	0	0	None	0	5.64E-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
V/A	0.2606	likely_benign	0.2439	benign	-0.887	Destabilizing	0.63	D	0.454	neutral	N	0.394042507	None	None	I
V/C	0.6985	likely_pathogenic	0.6894	pathogenic	-0.761	Destabilizing	0.073	N	0.402	neutral	None	None	None	None	I
V/D	0.5376	ambiguous	0.5193	ambiguous	-0.437	Destabilizing	0.994	D	0.719	prob.delet.	N	0.414241634	None	None	I
V/E	0.4623	ambiguous	0.4654	ambiguous	-0.522	Destabilizing	0.996	D	0.665	neutral	None	None	None	None	I
V/F	0.2855	likely_benign	0.2912	benign	-0.946	Destabilizing	0.983	D	0.641	neutral	N	0.505346428	None	None	I
V/G	0.3029	likely_benign	0.2692	benign	-1.086	Destabilizing	0.983	D	0.697	prob.neutral	N	0.385999027	None	None	I
V/H	0.7547	likely_pathogenic	0.7307	pathogenic	-0.622	Destabilizing	0.999	D	0.722	prob.delet.	None	None	None	None	I
V/I	0.1005	likely_benign	0.1058	benign	-0.491	Destabilizing	0.773	D	0.483	neutral	N	0.505519786	None	None	I
V/K	0.5862	likely_pathogenic	0.5983	pathogenic	-0.654	Destabilizing	0.987	D	0.671	neutral	None	None	None	None	I
V/L	0.3216	likely_benign	0.3282	benign	-0.491	Destabilizing	0.63	D	0.469	neutral	N	0.457131194	None	None	I
V/M	0.1871	likely_benign	0.1905	benign	-0.39	Destabilizing	0.996	D	0.66	neutral	None	None	None	None	I
V/N	0.3241	likely_benign	0.3094	benign	-0.39	Destabilizing	0.996	D	0.72	prob.delet.	None	None	None	None	I
V/P	0.9521	likely_pathogenic	0.9396	pathogenic	-0.587	Destabilizing	0.996	D	0.682	prob.neutral	None	None	None	None	I
V/Q	0.4742	ambiguous	0.4783	ambiguous	-0.636	Destabilizing	0.996	D	0.683	prob.neutral	None	None	None	None	I
V/R	0.5638	ambiguous	0.5783	pathogenic	-0.125	Destabilizing	0.996	D	0.725	prob.delet.	None	None	None	None	I
V/S	0.2736	likely_benign	0.2574	benign	-0.856	Destabilizing	0.975	D	0.615	neutral	None	None	None	None	I
V/T	0.2077	likely_benign	0.2025	benign	-0.834	Destabilizing	0.916	D	0.518	neutral	None	None	None	None	I
V/W	0.9393	likely_pathogenic	0.934	pathogenic	-1.019	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	I
V/Y	0.681	likely_pathogenic	0.6732	pathogenic	-0.721	Destabilizing	0.996	D	0.651	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.