TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22834	68725;68726;68727	chr2:178578015;178578014;178578013	chr2:179442742;179442741;179442740
N2AB	21193	63802;63803;63804	chr2:178578015;178578014;178578013	chr2:179442742;179442741;179442740
N2A	20266	61021;61022;61023	chr2:178578015;178578014;178578013	chr2:179442742;179442741;179442740
N2B	13769	41530;41531;41532	chr2:178578015;178578014;178578013	chr2:179442742;179442741;179442740
Novex-1	13894	41905;41906;41907	chr2:178578015;178578014;178578013	chr2:179442742;179442741;179442740
Novex-2	13961	42106;42107;42108	chr2:178578015;178578014;178578013	chr2:179442742;179442741;179442740
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-53
• Domain position: 92
• Structural Position: 125
• Q(SASA): 0.7474
• 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
E/Q	rs557161476	0.385	0.999	N	0.618	0.188	0.222439326576	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	1.93274E-04	None	0	0	0	0	0
E/Q	rs557161476	0.385	0.999	N	0.618	0.188	0.222439326576	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	0	None	None	1E-03	0	None	None	None	0	None
E/Q	rs557161476	0.385	0.999	N	0.618	0.188	0.222439326576	gnomAD-4.0.0	2.56394E-06	None	None	None	None	I	None	0	0	None	0	4.86642E-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
E/A	0.1482	likely_benign	0.1546	benign	-0.111	Destabilizing	0.996	D	0.612	neutral	N	0.484691515	None	None	I
E/C	0.8091	likely_pathogenic	0.8113	pathogenic	-0.251	Destabilizing	1.0	D	0.703	prob.delet.	None	None	None	None	I
E/D	0.0943	likely_benign	0.0967	benign	-0.243	Destabilizing	0.996	D	0.473	neutral	N	0.438420508	None	None	I
E/F	0.6897	likely_pathogenic	0.6971	pathogenic	-0.066	Destabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	I
E/G	0.1731	likely_benign	0.1767	benign	-0.246	Destabilizing	0.999	D	0.467	neutral	N	0.466009506	None	None	I
E/H	0.4387	ambiguous	0.4529	ambiguous	0.545	Stabilizing	0.522	D	0.501	neutral	None	None	None	None	I
E/I	0.297	likely_benign	0.2948	benign	0.194	Stabilizing	1.0	D	0.695	prob.delet.	None	None	None	None	I
E/K	0.1202	likely_benign	0.1198	benign	0.34	Stabilizing	0.996	D	0.525	neutral	N	0.509088527	None	None	I
E/L	0.3235	likely_benign	0.3308	benign	0.194	Stabilizing	0.999	D	0.651	prob.neutral	None	None	None	None	I
E/M	0.4012	ambiguous	0.3952	ambiguous	-0.022	Destabilizing	1.0	D	0.613	neutral	None	None	None	None	I
E/N	0.2071	likely_benign	0.2087	benign	0.071	Stabilizing	0.998	D	0.646	neutral	None	None	None	None	I
E/P	0.3318	likely_benign	0.347	ambiguous	0.111	Stabilizing	1.0	D	0.659	prob.neutral	None	None	None	None	I
E/Q	0.1319	likely_benign	0.1322	benign	0.095	Stabilizing	0.999	D	0.618	neutral	N	0.507125658	None	None	I
E/R	0.2322	likely_benign	0.2455	benign	0.634	Stabilizing	0.999	D	0.67	prob.neutral	None	None	None	None	I
E/S	0.1788	likely_benign	0.1796	benign	-0.092	Destabilizing	0.997	D	0.595	neutral	None	None	None	None	I
E/T	0.2109	likely_benign	0.2102	benign	0.027	Stabilizing	1.0	D	0.657	prob.neutral	None	None	None	None	I
E/V	0.1879	likely_benign	0.1881	benign	0.111	Stabilizing	1.0	D	0.615	neutral	N	0.471223292	None	None	I
E/W	0.8767	likely_pathogenic	0.8871	pathogenic	0.017	Stabilizing	1.0	D	0.703	prob.delet.	None	None	None	None	I
E/Y	0.5375	ambiguous	0.556	ambiguous	0.164	Stabilizing	0.998	D	0.605	neutral	None	None	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.