TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8068	24427;24428;24429	chr2:178719188;178719187;178719186	chr2:179583915;179583914;179583913
N2AB	7751	23476;23477;23478	chr2:178719188;178719187;178719186	chr2:179583915;179583914;179583913
N2A	6824	20695;20696;20697	chr2:178719188;178719187;178719186	chr2:179583915;179583914;179583913
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: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-65
• Domain position: 84
• Structural Position: 169
• Q(SASA): 0.1149
• 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
C/Y	None	None	0.484	N	0.785	0.28	0.772923806147	gnomAD-4.0.0	1.59219E-06	None	None	None	None	N	None	0	0	None	0	2.77331E-05	None	0	0	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
C/A	0.2881	likely_benign	0.2928	benign	-1.986	Destabilizing	0.016	N	0.441	neutral	None	None	None	None	N
C/D	0.7738	likely_pathogenic	0.744	pathogenic	-0.859	Destabilizing	0.081	N	0.794	deleterious	None	None	None	None	N
C/E	0.9068	likely_pathogenic	0.8855	pathogenic	-0.729	Destabilizing	0.081	N	0.801	deleterious	None	None	None	None	N
C/F	0.4738	ambiguous	0.4586	ambiguous	-1.239	Destabilizing	0.484	N	0.793	deleterious	N	0.485301163	None	None	N
C/G	0.1423	likely_benign	0.1548	benign	-2.317	Highly Destabilizing	None	N	0.553	neutral	N	0.491061608	None	None	N
C/H	0.7895	likely_pathogenic	0.7506	pathogenic	-2.28	Highly Destabilizing	0.824	D	0.773	deleterious	None	None	None	None	N
C/I	0.5902	likely_pathogenic	0.5842	pathogenic	-1.115	Destabilizing	0.38	N	0.786	deleterious	None	None	None	None	N
C/K	0.9505	likely_pathogenic	0.9341	pathogenic	-1.326	Destabilizing	0.081	N	0.803	deleterious	None	None	None	None	N
C/L	0.6081	likely_pathogenic	0.5932	pathogenic	-1.115	Destabilizing	0.149	N	0.707	prob.neutral	None	None	None	None	N
C/M	0.658	likely_pathogenic	0.6521	pathogenic	-0.034	Destabilizing	0.791	D	0.743	deleterious	None	None	None	None	N
C/N	0.4802	ambiguous	0.4493	ambiguous	-1.385	Destabilizing	0.081	N	0.806	deleterious	None	None	None	None	N
C/P	0.99	likely_pathogenic	0.9882	pathogenic	-1.381	Destabilizing	0.38	N	0.814	deleterious	None	None	None	None	N
C/Q	0.8417	likely_pathogenic	0.8104	pathogenic	-1.253	Destabilizing	0.38	N	0.818	deleterious	None	None	None	None	N
C/R	0.834	likely_pathogenic	0.7956	pathogenic	-1.202	Destabilizing	0.317	N	0.814	deleterious	D	0.532038037	None	None	N
C/S	0.1211	likely_benign	0.1238	benign	-1.929	Destabilizing	None	N	0.399	neutral	N	0.461791305	None	None	N
C/T	0.2016	likely_benign	0.2341	benign	-1.616	Destabilizing	0.002	N	0.426	neutral	None	None	None	None	N
C/V	0.4616	ambiguous	0.4439	ambiguous	-1.381	Destabilizing	0.149	N	0.721	prob.delet.	None	None	None	None	N
C/W	0.8058	likely_pathogenic	0.7776	pathogenic	-1.274	Destabilizing	0.915	D	0.73	prob.delet.	N	0.486884552	None	None	N
C/Y	0.5326	ambiguous	0.5006	ambiguous	-1.271	Destabilizing	0.484	N	0.785	deleterious	N	0.496910958	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.