TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31723	95392;95393;95394	chr2:178546069;178546068;178546067	chr2:179410796;179410795;179410794
N2AB	30082	90469;90470;90471	chr2:178546069;178546068;178546067	chr2:179410796;179410795;179410794
N2A	29155	87688;87689;87690	chr2:178546069;178546068;178546067	chr2:179410796;179410795;179410794
N2B	22658	68197;68198;68199	chr2:178546069;178546068;178546067	chr2:179410796;179410795;179410794
Novex-1	22783	68572;68573;68574	chr2:178546069;178546068;178546067	chr2:179410796;179410795;179410794
Novex-2	22850	68773;68774;68775	chr2:178546069;178546068;178546067	chr2:179410796;179410795;179410794
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-119
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.5037
• Predicted PPI site: N

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
E/K	rs1225039103	-0.021	0.999	N	0.579	0.4	0.355450299083	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/K	rs1225039103	-0.021	0.999	N	0.579	0.4	0.355450299083	gnomAD-4.0.0	1.59239E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43349E-05	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
E/A	0.6694	likely_pathogenic	0.6563	pathogenic	-0.734	Destabilizing	0.999	D	0.662	neutral	N	0.478521581	None	None	N
E/C	0.9864	likely_pathogenic	0.9838	pathogenic	-0.234	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
E/D	0.1895	likely_benign	0.1698	benign	-0.833	Destabilizing	0.999	D	0.483	neutral	N	0.460046574	None	None	N
E/F	0.977	likely_pathogenic	0.9748	pathogenic	-0.561	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
E/G	0.5021	ambiguous	0.4984	ambiguous	-1.015	Destabilizing	1.0	D	0.675	prob.neutral	N	0.469127059	None	None	N
E/H	0.9067	likely_pathogenic	0.8931	pathogenic	-0.766	Destabilizing	1.0	D	0.608	neutral	None	None	None	None	N
E/I	0.9061	likely_pathogenic	0.9018	pathogenic	0.004	Stabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
E/K	0.6829	likely_pathogenic	0.6814	pathogenic	-0.254	Destabilizing	0.999	D	0.579	neutral	N	0.473646509	None	None	N
E/L	0.8827	likely_pathogenic	0.8781	pathogenic	0.004	Stabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
E/M	0.8981	likely_pathogenic	0.8944	pathogenic	0.386	Stabilizing	1.0	D	0.617	neutral	None	None	None	None	N
E/N	0.6126	likely_pathogenic	0.5874	pathogenic	-0.56	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
E/P	0.9899	likely_pathogenic	0.9891	pathogenic	-0.221	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
E/Q	0.4818	ambiguous	0.4787	ambiguous	-0.514	Destabilizing	1.0	D	0.613	neutral	N	0.472596552	None	None	N
E/R	0.8161	likely_pathogenic	0.8082	pathogenic	-0.095	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	N
E/S	0.6614	likely_pathogenic	0.6499	pathogenic	-0.806	Destabilizing	0.999	D	0.628	neutral	None	None	None	None	N
E/T	0.6878	likely_pathogenic	0.6572	pathogenic	-0.583	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
E/V	0.7787	likely_pathogenic	0.7667	pathogenic	-0.221	Destabilizing	1.0	D	0.705	prob.neutral	N	0.495727237	None	None	N
E/W	0.988	likely_pathogenic	0.9875	pathogenic	-0.388	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
E/Y	0.939	likely_pathogenic	0.9326	pathogenic	-0.323	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N

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.