TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33433	100522;100523;100524	chr2:178536450;178536449;178536448	chr2:179401177;179401176;179401175
N2AB	31792	95599;95600;95601	chr2:178536450;178536449;178536448	chr2:179401177;179401176;179401175
N2A	30865	92818;92819;92820	chr2:178536450;178536449;178536448	chr2:179401177;179401176;179401175
N2B	24368	73327;73328;73329	chr2:178536450;178536449;178536448	chr2:179401177;179401176;179401175
Novex-1	24493	73702;73703;73704	chr2:178536450;178536449;178536448	chr2:179401177;179401176;179401175
Novex-2	24560	73903;73904;73905	chr2:178536450;178536449;178536448	chr2:179401177;179401176;179401175
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: Fn3-131
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.3239
• 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	rs879015914	-1.188	0.275	N	0.186	0.038	0.289474373501	gnomAD-2.1.1	2.03E-05	None	None	None	None	N	None	2.58766E-04	0	None	0	0	None	0	None	0	0	1.67448E-04
E/D	rs879015914	-1.188	0.275	N	0.186	0.038	0.289474373501	gnomAD-3.1.2	5.26E-05	None	None	None	None	N	None	1.92911E-04	0	0	0	0	None	0	0	0	0	0
E/D	rs879015914	-1.188	0.275	N	0.186	0.038	0.289474373501	gnomAD-4.0.0	7.4495E-06	None	None	None	None	N	None	1.47141E-04	0	None	0	0	None	0	0	0	0	1.60426E-05

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	0.5595	ambiguous	0.5976	pathogenic	-0.764	Destabilizing	0.996	D	0.596	neutral	N	0.473396701	None	None	N
E/C	0.9653	likely_pathogenic	0.9629	pathogenic	-0.568	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/D	0.4427	ambiguous	0.4252	ambiguous	-1.344	Destabilizing	0.275	N	0.186	neutral	N	0.46145487	None	None	N
E/F	0.9698	likely_pathogenic	0.9728	pathogenic	0.019	Stabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
E/G	0.5363	ambiguous	0.5973	pathogenic	-1.189	Destabilizing	0.998	D	0.675	neutral	N	0.489387815	None	None	N
E/H	0.903	likely_pathogenic	0.9026	pathogenic	-0.337	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
E/I	0.8348	likely_pathogenic	0.8508	pathogenic	0.417	Stabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
E/K	0.6728	likely_pathogenic	0.7395	pathogenic	-0.959	Destabilizing	0.992	D	0.509	neutral	N	0.477114969	None	None	N
E/L	0.8202	likely_pathogenic	0.8408	pathogenic	0.417	Stabilizing	0.999	D	0.806	deleterious	None	None	None	None	N
E/M	0.8764	likely_pathogenic	0.8865	pathogenic	0.888	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
E/N	0.7405	likely_pathogenic	0.7534	pathogenic	-1.499	Destabilizing	0.998	D	0.671	neutral	None	None	None	None	N
E/P	0.8956	likely_pathogenic	0.9229	pathogenic	0.045	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/Q	0.4845	ambiguous	0.5234	ambiguous	-1.282	Destabilizing	0.999	D	0.63	neutral	N	0.472609779	None	None	N
E/R	0.8084	likely_pathogenic	0.8411	pathogenic	-0.64	Destabilizing	0.999	D	0.736	prob.delet.	None	None	None	None	N
E/S	0.697	likely_pathogenic	0.7204	pathogenic	-1.869	Destabilizing	0.994	D	0.556	neutral	None	None	None	None	N
E/T	0.7939	likely_pathogenic	0.8191	pathogenic	-1.509	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	N
E/V	0.6831	likely_pathogenic	0.7093	pathogenic	0.045	Stabilizing	1.0	D	0.778	deleterious	N	0.479512767	None	None	N
E/W	0.9876	likely_pathogenic	0.989	pathogenic	0.227	Stabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
E/Y	0.9469	likely_pathogenic	0.9528	pathogenic	0.248	Stabilizing	1.0	D	0.782	deleterious	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.