TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15944	48055;48056;48057	chr2:178617165;178617164;178617163	chr2:179481892;179481891;179481890
N2AB	14303	43132;43133;43134	chr2:178617165;178617164;178617163	chr2:179481892;179481891;179481890
N2A	13376	40351;40352;40353	chr2:178617165;178617164;178617163	chr2:179481892;179481891;179481890
N2B	6879	20860;20861;20862	chr2:178617165;178617164;178617163	chr2:179481892;179481891;179481890
Novex-1	7004	21235;21236;21237	chr2:178617165;178617164;178617163	chr2:179481892;179481891;179481890
Novex-2	7071	21436;21437;21438	chr2:178617165;178617164;178617163	chr2:179481892;179481891;179481890
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: 86
• Structural Position: 119
• Q(SASA): 0.3637
• 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/N	None	None	0.999	N	0.741	0.277	0.277317399466	gnomAD-4.0.0	1.614E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.46361E-05	0
D/V	rs1442512599	0.007	0.999	N	0.779	0.521	0.59676212909	gnomAD-4.0.0	1.61302E-06	None	None	None	None	I	None	0	0	None	4.81047E-05	0	None	0	0	0	0	0
D/Y	None	None	1.0	D	0.782	0.399	0.647688206944	gnomAD-4.0.0	1.614E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.46361E-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	0.2676	likely_benign	0.1957	benign	-0.36	Destabilizing	0.996	D	0.761	deleterious	N	0.478382427	None	None	I
D/C	0.807	likely_pathogenic	0.6962	pathogenic	0.173	Stabilizing	1.0	D	0.772	deleterious	None	None	None	None	I
D/E	0.1871	likely_benign	0.1374	benign	-0.343	Destabilizing	0.996	D	0.545	neutral	N	0.432268265	None	None	I
D/F	0.699	likely_pathogenic	0.5738	pathogenic	-0.465	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
D/G	0.3804	ambiguous	0.296	benign	-0.528	Destabilizing	0.998	D	0.757	deleterious	N	0.45958717	None	None	I
D/H	0.456	ambiguous	0.3686	ambiguous	-0.39	Destabilizing	1.0	D	0.726	prob.delet.	N	0.511974871	None	None	I
D/I	0.4538	ambiguous	0.3533	ambiguous	0.028	Stabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
D/K	0.4433	ambiguous	0.3625	ambiguous	0.4	Stabilizing	0.91	D	0.482	neutral	None	None	None	None	I
D/L	0.4374	ambiguous	0.3539	ambiguous	0.028	Stabilizing	1.0	D	0.786	deleterious	None	None	None	None	I
D/M	0.7035	likely_pathogenic	0.5857	pathogenic	0.294	Stabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
D/N	0.1825	likely_benign	0.1511	benign	0.161	Stabilizing	0.999	D	0.741	deleterious	N	0.504939443	None	None	I
D/P	0.6437	likely_pathogenic	0.5358	ambiguous	-0.08	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
D/Q	0.4351	ambiguous	0.3449	ambiguous	0.16	Stabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	I
D/R	0.5461	ambiguous	0.4651	ambiguous	0.438	Stabilizing	0.998	D	0.799	deleterious	None	None	None	None	I
D/S	0.2089	likely_benign	0.1675	benign	0.072	Stabilizing	0.997	D	0.7	prob.neutral	None	None	None	None	I
D/T	0.3966	ambiguous	0.2994	benign	0.201	Stabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
D/V	0.3037	likely_benign	0.2228	benign	-0.08	Destabilizing	0.999	D	0.779	deleterious	N	0.473328214	None	None	I
D/W	0.9241	likely_pathogenic	0.8846	pathogenic	-0.361	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
D/Y	0.3411	ambiguous	0.2685	benign	-0.233	Destabilizing	1.0	D	0.782	deleterious	D	0.578994642	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.