TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20183	60772;60773;60774	chr2:178591178;178591177;178591176	chr2:179455905;179455904;179455903
N2AB	18542	55849;55850;55851	chr2:178591178;178591177;178591176	chr2:179455905;179455904;179455903
N2A	17615	53068;53069;53070	chr2:178591178;178591177;178591176	chr2:179455905;179455904;179455903
N2B	11118	33577;33578;33579	chr2:178591178;178591177;178591176	chr2:179455905;179455904;179455903
Novex-1	11243	33952;33953;33954	chr2:178591178;178591177;178591176	chr2:179455905;179455904;179455903
Novex-2	11310	34153;34154;34155	chr2:178591178;178591177;178591176	chr2:179455905;179455904;179455903
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-34
• Domain position: 13
• Structural Position: 14
• Q(SASA): 0.5454
• 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
D/G	None	None	0.117	N	0.379	0.244	0.218845423259	gnomAD-4.0.0	1.5921E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43312E-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
D/A	0.1788	likely_benign	0.1601	benign	-0.534	Destabilizing	0.062	N	0.394	neutral	N	0.511880903	None	None	N
D/C	0.6783	likely_pathogenic	0.6656	pathogenic	-0.262	Destabilizing	0.935	D	0.516	neutral	None	None	None	None	N
D/E	0.1176	likely_benign	0.0941	benign	-0.636	Destabilizing	None	N	0.064	neutral	N	0.398518112	None	None	N
D/F	0.7291	likely_pathogenic	0.7181	pathogenic	-0.378	Destabilizing	0.791	D	0.465	neutral	None	None	None	None	N
D/G	0.2345	likely_benign	0.2187	benign	-0.816	Destabilizing	0.117	N	0.379	neutral	N	0.511227542	None	None	N
D/H	0.3053	likely_benign	0.3069	benign	-0.623	Destabilizing	0.484	N	0.399	neutral	N	0.482626639	None	None	N
D/I	0.51	ambiguous	0.4865	ambiguous	0.186	Stabilizing	0.555	D	0.472	neutral	None	None	None	None	N
D/K	0.4524	ambiguous	0.42	ambiguous	-0.53	Destabilizing	0.081	N	0.365	neutral	None	None	None	None	N
D/L	0.4359	ambiguous	0.4002	ambiguous	0.186	Stabilizing	0.38	N	0.421	neutral	None	None	None	None	N
D/M	0.6333	likely_pathogenic	0.5925	pathogenic	0.513	Stabilizing	0.935	D	0.452	neutral	None	None	None	None	N
D/N	0.1447	likely_benign	0.1382	benign	-0.735	Destabilizing	0.117	N	0.387	neutral	N	0.483520866	None	None	N
D/P	0.9256	likely_pathogenic	0.915	pathogenic	-0.031	Destabilizing	0.555	D	0.389	neutral	None	None	None	None	N
D/Q	0.3318	likely_benign	0.2979	benign	-0.647	Destabilizing	0.081	N	0.329	neutral	None	None	None	None	N
D/R	0.4801	ambiguous	0.4682	ambiguous	-0.33	Destabilizing	0.235	N	0.405	neutral	None	None	None	None	N
D/S	0.1444	likely_benign	0.1377	benign	-0.932	Destabilizing	0.081	N	0.353	neutral	None	None	None	None	N
D/T	0.2687	likely_benign	0.2559	benign	-0.725	Destabilizing	0.149	N	0.403	neutral	None	None	None	None	N
D/V	0.2894	likely_benign	0.2783	benign	-0.031	Destabilizing	0.317	N	0.432	neutral	N	0.481359191	None	None	N
D/W	0.8942	likely_pathogenic	0.8921	pathogenic	-0.272	Destabilizing	0.935	D	0.581	neutral	None	None	None	None	N
D/Y	0.339	likely_benign	0.3486	ambiguous	-0.194	Destabilizing	0.741	D	0.466	neutral	N	0.48624749	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.