TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31057	93394;93395;93396	chr2:178548457;178548456;178548455	chr2:179413184;179413183;179413182
N2AB	29416	88471;88472;88473	chr2:178548457;178548456;178548455	chr2:179413184;179413183;179413182
N2A	28489	85690;85691;85692	chr2:178548457;178548456;178548455	chr2:179413184;179413183;179413182
N2B	21992	66199;66200;66201	chr2:178548457;178548456;178548455	chr2:179413184;179413183;179413182
Novex-1	22117	66574;66575;66576	chr2:178548457;178548456;178548455	chr2:179413184;179413183;179413182
Novex-2	22184	66775;66776;66777	chr2:178548457;178548456;178548455	chr2:179413184;179413183;179413182
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: Fn3-114
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.1932
• 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	rs759940210	None	0.999	N	0.494	0.173	0.254244900254	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07555E-04	0
E/D	rs759940210	None	0.999	N	0.494	0.173	0.254244900254	gnomAD-4.0.0	1.85904E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	3.29395E-05	0
E/G	rs1353038457	None	1.0	N	0.704	0.559	0.603539076606	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.9305E-04	None	0	0	0	0	0
E/G	rs1353038457	None	1.0	N	0.704	0.559	0.603539076606	gnomAD-4.0.0	6.5741E-06	None	None	None	None	N	None	0	0	None	0	1.9305E-04	None	0	0	0	0	0
E/K	rs767977295	-0.556	0.999	N	0.581	0.416	0.486422812247	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
E/K	rs767977295	-0.556	0.999	N	0.581	0.416	0.486422812247	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs767977295	-0.556	0.999	N	0.581	0.416	0.486422812247	gnomAD-4.0.0	6.57125E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46981E-05	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	0.6397	likely_pathogenic	0.5787	pathogenic	-0.769	Destabilizing	0.999	D	0.665	neutral	N	0.492488461	None	None	N
E/C	0.9869	likely_pathogenic	0.9823	pathogenic	-0.506	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
E/D	0.369	ambiguous	0.3368	benign	-1.424	Destabilizing	0.999	D	0.494	neutral	N	0.459569358	None	None	N
E/F	0.9849	likely_pathogenic	0.981	pathogenic	-0.049	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/G	0.7668	likely_pathogenic	0.7314	pathogenic	-1.203	Destabilizing	1.0	D	0.704	prob.neutral	N	0.497617022	None	None	N
E/H	0.9463	likely_pathogenic	0.9307	pathogenic	-0.372	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	N
E/I	0.9011	likely_pathogenic	0.8714	pathogenic	0.436	Stabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
E/K	0.8257	likely_pathogenic	0.7704	pathogenic	-0.9	Destabilizing	0.999	D	0.581	neutral	N	0.47145769	None	None	N
E/L	0.8708	likely_pathogenic	0.8434	pathogenic	0.436	Stabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
E/M	0.8986	likely_pathogenic	0.8681	pathogenic	0.954	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
E/N	0.8408	likely_pathogenic	0.809	pathogenic	-1.441	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
E/P	0.9298	likely_pathogenic	0.9039	pathogenic	0.056	Stabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
E/Q	0.6142	likely_pathogenic	0.5456	ambiguous	-1.226	Destabilizing	1.0	D	0.618	neutral	N	0.491701539	None	None	N
E/R	0.9074	likely_pathogenic	0.8691	pathogenic	-0.6	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
E/S	0.7932	likely_pathogenic	0.7594	pathogenic	-1.84	Destabilizing	0.999	D	0.62	neutral	None	None	None	None	N
E/T	0.854	likely_pathogenic	0.8233	pathogenic	-1.471	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
E/V	0.7687	likely_pathogenic	0.7139	pathogenic	0.056	Stabilizing	1.0	D	0.788	deleterious	N	0.498769111	None	None	N
E/W	0.9952	likely_pathogenic	0.9939	pathogenic	0.141	Stabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
E/Y	0.9745	likely_pathogenic	0.9695	pathogenic	0.196	Stabilizing	1.0	D	0.789	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.