TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18851	56776;56777;56778	chr2:178599242;178599241;178599240	chr2:179463969;179463968;179463967
N2AB	17210	51853;51854;51855	chr2:178599242;178599241;178599240	chr2:179463969;179463968;179463967
N2A	16283	49072;49073;49074	chr2:178599242;178599241;178599240	chr2:179463969;179463968;179463967
N2B	9786	29581;29582;29583	chr2:178599242;178599241;178599240	chr2:179463969;179463968;179463967
Novex-1	9911	29956;29957;29958	chr2:178599242;178599241;178599240	chr2:179463969;179463968;179463967
Novex-2	9978	30157;30158;30159	chr2:178599242;178599241;178599240	chr2:179463969;179463968;179463967
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-24
• Domain position: 68
• Structural Position: 99
• Q(SASA): 0.5
• 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
E/D	None	None	0.963	N	0.529	0.251	0.301455362545	gnomAD-4.0.0	1.75616E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.94977E-05	0	0	0	0
E/Q	rs1347369638	None	0.989	N	0.653	0.283	0.254244900254	gnomAD-4.0.0	7.12769E-07	None	None	None	None	N	None	3.20718E-05	0	None	0	0	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
E/A	0.1553	likely_benign	0.1901	benign	-0.586	Destabilizing	0.039	N	0.277	neutral	N	0.520441672	None	None	N
E/C	0.8821	likely_pathogenic	0.9038	pathogenic	-0.113	Destabilizing	0.998	D	0.699	prob.neutral	None	None	None	None	N
E/D	0.2488	likely_benign	0.2674	benign	-0.58	Destabilizing	0.963	D	0.529	neutral	N	0.485651606	None	None	N
E/F	0.8889	likely_pathogenic	0.9168	pathogenic	-0.465	Destabilizing	0.992	D	0.693	prob.neutral	None	None	None	None	N
E/G	0.2978	likely_benign	0.3742	ambiguous	-0.829	Destabilizing	0.865	D	0.553	neutral	N	0.497261401	None	None	N
E/H	0.6221	likely_pathogenic	0.6751	pathogenic	-0.49	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
E/I	0.4923	ambiguous	0.5623	ambiguous	0.036	Stabilizing	0.983	D	0.675	prob.neutral	None	None	None	None	N
E/K	0.2106	likely_benign	0.2517	benign	-0.039	Destabilizing	0.928	D	0.586	neutral	N	0.518404231	None	None	N
E/L	0.5239	ambiguous	0.6139	pathogenic	0.036	Stabilizing	0.968	D	0.622	neutral	None	None	None	None	N
E/M	0.6077	likely_pathogenic	0.6808	pathogenic	0.311	Stabilizing	0.999	D	0.632	neutral	None	None	None	None	N
E/N	0.4867	ambiguous	0.5261	ambiguous	-0.304	Destabilizing	0.992	D	0.645	neutral	None	None	None	None	N
E/P	0.348	ambiguous	0.4155	ambiguous	-0.151	Destabilizing	0.992	D	0.606	neutral	None	None	None	None	N
E/Q	0.1638	likely_benign	0.1929	benign	-0.262	Destabilizing	0.989	D	0.653	neutral	N	0.517769513	None	None	N
E/R	0.3397	likely_benign	0.3953	ambiguous	0.153	Stabilizing	0.983	D	0.644	neutral	None	None	None	None	N
E/S	0.3112	likely_benign	0.3518	ambiguous	-0.513	Destabilizing	0.895	D	0.549	neutral	None	None	None	None	N
E/T	0.3082	likely_benign	0.3619	ambiguous	-0.324	Destabilizing	0.983	D	0.573	neutral	None	None	None	None	N
E/V	0.2709	likely_benign	0.3289	benign	-0.151	Destabilizing	0.957	D	0.574	neutral	N	0.487791199	None	None	N
E/W	0.9565	likely_pathogenic	0.9711	pathogenic	-0.311	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
E/Y	0.7906	likely_pathogenic	0.8293	pathogenic	-0.234	Destabilizing	0.997	D	0.656	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.