TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3866	11821;11822;11823	chr2:178741637;178741636;178741635	chr2:179606364;179606363;179606362
N2AB	3549	10870;10871;10872	chr2:178741637;178741636;178741635	chr2:179606364;179606363;179606362
N2A	None	None	chr2:None	chr2:None
N2B	3503	10732;10733;10734	chr2:178741637;178741636;178741635	chr2:179606364;179606363;179606362
Novex-1	3628	11107;11108;11109	chr2:178741637;178741636;178741635	chr2:179606364;179606363;179606362
Novex-2	3695	11308;11309;11310	chr2:178741637;178741636;178741635	chr2:179606364;179606363;179606362
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-27
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.1695
• 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
Y/H	rs777421661	-1.949	0.002	N	0.296	0.175	None	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	1.11458E-04	None	0	None	0	0	0
Y/H	rs777421661	-1.949	0.002	N	0.296	0.175	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92604E-04	None	0	0	0	0	0
Y/H	rs777421661	-1.949	0.002	N	0.296	0.175	None	gnomAD-4.0.0	1.85889E-06	None	None	None	None	N	None	0	0	None	0	6.68717E-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
Y/A	0.8134	likely_pathogenic	0.6679	pathogenic	-2.704	Highly Destabilizing	0.157	N	0.611	neutral	None	None	None	None	N
Y/C	0.1461	likely_benign	0.1099	benign	-1.887	Destabilizing	0.001	N	0.403	neutral	D	0.58001381	None	None	N
Y/D	0.7798	likely_pathogenic	0.5693	pathogenic	-1.957	Destabilizing	0.667	D	0.737	prob.delet.	D	0.548569147	None	None	N
Y/E	0.8926	likely_pathogenic	0.7707	pathogenic	-1.764	Destabilizing	0.567	D	0.672	neutral	None	None	None	None	N
Y/F	0.1855	likely_benign	0.1746	benign	-0.997	Destabilizing	0.364	N	0.559	neutral	N	0.487846258	None	None	N
Y/G	0.7403	likely_pathogenic	0.5911	pathogenic	-3.129	Highly Destabilizing	0.567	D	0.681	prob.neutral	None	None	None	None	N
Y/H	0.2866	likely_benign	0.1868	benign	-1.655	Destabilizing	0.002	N	0.296	neutral	N	0.514569717	None	None	N
Y/I	0.7068	likely_pathogenic	0.5692	pathogenic	-1.34	Destabilizing	0.567	D	0.651	neutral	None	None	None	None	N
Y/K	0.78	likely_pathogenic	0.6181	pathogenic	-1.978	Destabilizing	0.567	D	0.687	prob.neutral	None	None	None	None	N
Y/L	0.6656	likely_pathogenic	0.5554	ambiguous	-1.34	Destabilizing	0.157	N	0.574	neutral	None	None	None	None	N
Y/M	0.8109	likely_pathogenic	0.7227	pathogenic	-1.228	Destabilizing	0.968	D	0.667	neutral	None	None	None	None	N
Y/N	0.4287	ambiguous	0.2728	benign	-2.618	Highly Destabilizing	0.497	N	0.709	prob.delet.	D	0.580159117	None	None	N
Y/P	0.9844	likely_pathogenic	0.9628	pathogenic	-1.802	Destabilizing	0.89	D	0.771	deleterious	None	None	None	None	N
Y/Q	0.7464	likely_pathogenic	0.575	pathogenic	-2.323	Highly Destabilizing	0.726	D	0.7	prob.neutral	None	None	None	None	N
Y/R	0.5465	ambiguous	0.3868	ambiguous	-1.808	Destabilizing	0.567	D	0.719	prob.delet.	None	None	None	None	N
Y/S	0.4869	ambiguous	0.3012	benign	-3.191	Highly Destabilizing	0.497	N	0.645	neutral	N	0.510149362	None	None	N
Y/T	0.7115	likely_pathogenic	0.5295	ambiguous	-2.871	Highly Destabilizing	0.567	D	0.659	neutral	None	None	None	None	N
Y/V	0.5811	likely_pathogenic	0.4626	ambiguous	-1.802	Destabilizing	0.157	N	0.597	neutral	None	None	None	None	N
Y/W	0.6179	likely_pathogenic	0.5474	ambiguous	-0.357	Destabilizing	0.968	D	0.591	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.