TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15160	45703;45704;45705	chr2:178621240;178621239;178621238	chr2:179485967;179485966;179485965
N2AB	13519	40780;40781;40782	chr2:178621240;178621239;178621238	chr2:179485967;179485966;179485965
N2A	12592	37999;38000;38001	chr2:178621240;178621239;178621238	chr2:179485967;179485966;179485965
N2B	6095	18508;18509;18510	chr2:178621240;178621239;178621238	chr2:179485967;179485966;179485965
Novex-1	6220	18883;18884;18885	chr2:178621240;178621239;178621238	chr2:179485967;179485966;179485965
Novex-2	6287	19084;19085;19086	chr2:178621240;178621239;178621238	chr2:179485967;179485966;179485965
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: Ig-103
• Domain position: 41
• Structural Position: 59
• Q(SASA): 0.7694
• 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/K	None	0.831	0.956	N	0.584	0.277	0.392855499163	gnomAD-4.0.0	1.59424E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88466E-05	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	0.1281	likely_benign	0.1237	benign	0.003	Stabilizing	0.978	D	0.565	neutral	N	0.509736654	None	None	N
E/C	0.8479	likely_pathogenic	0.7648	pathogenic	-0.222	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
E/D	0.1171	likely_benign	0.1128	benign	-0.333	Destabilizing	0.978	D	0.536	neutral	N	0.513098491	None	None	N
E/F	0.6771	likely_pathogenic	0.6248	pathogenic	0.073	Stabilizing	0.998	D	0.649	neutral	None	None	None	None	N
E/G	0.1764	likely_benign	0.1663	benign	-0.13	Destabilizing	0.997	D	0.526	neutral	N	0.512732126	None	None	N
E/H	0.4323	ambiguous	0.3578	ambiguous	0.677	Stabilizing	0.999	D	0.574	neutral	None	None	None	None	N
E/I	0.2547	likely_benign	0.2469	benign	0.3	Stabilizing	0.99	D	0.598	neutral	None	None	None	None	N
E/K	0.1543	likely_benign	0.1368	benign	0.497	Stabilizing	0.956	D	0.584	neutral	N	0.49828695	None	None	N
E/L	0.31	likely_benign	0.2784	benign	0.3	Stabilizing	0.967	D	0.581	neutral	None	None	None	None	N
E/M	0.4157	ambiguous	0.3805	ambiguous	0.039	Stabilizing	0.999	D	0.594	neutral	None	None	None	None	N
E/N	0.2149	likely_benign	0.2172	benign	0.074	Stabilizing	0.998	D	0.588	neutral	None	None	None	None	N
E/P	0.4242	ambiguous	0.4153	ambiguous	0.219	Stabilizing	0.999	D	0.605	neutral	None	None	None	None	N
E/Q	0.1301	likely_benign	0.1132	benign	0.121	Stabilizing	0.798	D	0.309	neutral	N	0.497950928	None	None	N
E/R	0.2946	likely_benign	0.2285	benign	0.742	Stabilizing	0.995	D	0.582	neutral	None	None	None	None	N
E/S	0.1678	likely_benign	0.1595	benign	-0.015	Destabilizing	0.983	D	0.575	neutral	None	None	None	None	N
E/T	0.1561	likely_benign	0.1536	benign	0.111	Stabilizing	0.983	D	0.569	neutral	None	None	None	None	N
E/V	0.1457	likely_benign	0.1416	benign	0.219	Stabilizing	0.576	D	0.377	neutral	N	0.514669587	None	None	N
E/W	0.9083	likely_pathogenic	0.8576	pathogenic	0.147	Stabilizing	1.0	D	0.671	neutral	None	None	None	None	N
E/Y	0.5968	likely_pathogenic	0.5385	ambiguous	0.304	Stabilizing	0.999	D	0.611	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.