TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15886	47881;47882;47883	chr2:178617429;178617428;178617427	chr2:179482156;179482155;179482154
N2AB	14245	42958;42959;42960	chr2:178617429;178617428;178617427	chr2:179482156;179482155;179482154
N2A	13318	40177;40178;40179	chr2:178617429;178617428;178617427	chr2:179482156;179482155;179482154
N2B	6821	20686;20687;20688	chr2:178617429;178617428;178617427	chr2:179482156;179482155;179482154
Novex-1	6946	21061;21062;21063	chr2:178617429;178617428;178617427	chr2:179482156;179482155;179482154
Novex-2	7013	21262;21263;21264	chr2:178617429;178617428;178617427	chr2:179482156;179482155;179482154
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: Fn3-3
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.2346
• 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
D/E	rs1451730427	-0.651	0.91	D	0.493	0.263	0.454054078574	gnomAD-2.1.1	4.43E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	9.54E-06	0
D/E	rs1451730427	-0.651	0.91	D	0.493	0.263	0.454054078574	gnomAD-4.0.0	1.64171E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.90688E-06	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
D/A	0.6823	likely_pathogenic	0.8109	pathogenic	-0.507	Destabilizing	0.98	D	0.663	neutral	D	0.565737561	None	None	I
D/C	0.9338	likely_pathogenic	0.9651	pathogenic	-0.047	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
D/E	0.7091	likely_pathogenic	0.8266	pathogenic	-0.641	Destabilizing	0.91	D	0.493	neutral	D	0.550334045	None	None	I
D/F	0.9438	likely_pathogenic	0.9715	pathogenic	-0.574	Destabilizing	0.999	D	0.756	deleterious	None	None	None	None	I
D/G	0.589	likely_pathogenic	0.7216	pathogenic	-0.783	Destabilizing	0.961	D	0.569	neutral	D	0.620918012	None	None	I
D/H	0.8182	likely_pathogenic	0.875	pathogenic	-0.942	Destabilizing	0.994	D	0.688	prob.neutral	D	0.635946004	None	None	I
D/I	0.8842	likely_pathogenic	0.9504	pathogenic	0.197	Stabilizing	0.999	D	0.761	deleterious	None	None	None	None	I
D/K	0.9128	likely_pathogenic	0.9553	pathogenic	-0.135	Destabilizing	0.97	D	0.593	neutral	None	None	None	None	I
D/L	0.8776	likely_pathogenic	0.9412	pathogenic	0.197	Stabilizing	0.996	D	0.743	deleterious	None	None	None	None	I
D/M	0.9464	likely_pathogenic	0.9756	pathogenic	0.666	Stabilizing	1.0	D	0.748	deleterious	None	None	None	None	I
D/N	0.1414	likely_benign	0.181	benign	-0.43	Destabilizing	0.122	N	0.187	neutral	N	0.480061178	None	None	I
D/P	0.9444	likely_pathogenic	0.9635	pathogenic	-0.014	Destabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	I
D/Q	0.9003	likely_pathogenic	0.9444	pathogenic	-0.354	Destabilizing	0.996	D	0.621	neutral	None	None	None	None	I
D/R	0.9286	likely_pathogenic	0.9595	pathogenic	-0.175	Destabilizing	0.996	D	0.718	prob.delet.	None	None	None	None	I
D/S	0.3983	ambiguous	0.5158	ambiguous	-0.614	Destabilizing	0.97	D	0.549	neutral	None	None	None	None	I
D/T	0.6106	likely_pathogenic	0.7687	pathogenic	-0.39	Destabilizing	0.97	D	0.595	neutral	None	None	None	None	I
D/V	0.7524	likely_pathogenic	0.8754	pathogenic	-0.014	Destabilizing	0.998	D	0.753	deleterious	D	0.61218926	None	None	I
D/W	0.987	likely_pathogenic	0.9915	pathogenic	-0.501	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
D/Y	0.6357	likely_pathogenic	0.7514	pathogenic	-0.359	Destabilizing	0.998	D	0.757	deleterious	D	0.697521741	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.