TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35331	106216;106217;106218	chr2:178530624;178530623;178530622	chr2:179395351;179395350;179395349
N2AB	33690	101293;101294;101295	chr2:178530624;178530623;178530622	chr2:179395351;179395350;179395349
N2A	32763	98512;98513;98514	chr2:178530624;178530623;178530622	chr2:179395351;179395350;179395349
N2B	26266	79021;79022;79023	chr2:178530624;178530623;178530622	chr2:179395351;179395350;179395349
Novex-1	26391	79396;79397;79398	chr2:178530624;178530623;178530622	chr2:179395351;179395350;179395349
Novex-2	26458	79597;79598;79599	chr2:178530624;178530623;178530622	chr2:179395351;179395350;179395349
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-165
• Domain position: 46
• Structural Position: 115
• Q(SASA): 0.167
• 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
H/N	rs753993485	-0.579	0.99	N	0.427	0.446	0.363158594168	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
H/N	rs753993485	-0.579	0.99	N	0.427	0.446	0.363158594168	gnomAD-4.0.0	1.59091E-06	None	None	None	None	N	None	0	2.28645E-05	None	0	0	None	0	0	0	0	0
H/Y	None	None	0.997	D	0.442	0.404	0.40417439687	gnomAD-4.0.0	1.59091E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-05	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
H/A	0.7187	likely_pathogenic	0.6512	pathogenic	-0.722	Destabilizing	0.993	D	0.423	neutral	None	None	None	None	N
H/C	0.3956	ambiguous	0.3336	benign	0.008	Stabilizing	1.0	D	0.613	neutral	None	None	None	None	N
H/D	0.555	ambiguous	0.503	ambiguous	-0.442	Destabilizing	0.997	D	0.372	neutral	N	0.495943951	None	None	N
H/E	0.7437	likely_pathogenic	0.6766	pathogenic	-0.354	Destabilizing	0.985	D	0.372	neutral	None	None	None	None	N
H/F	0.6476	likely_pathogenic	0.5913	pathogenic	0.281	Stabilizing	0.999	D	0.374	neutral	None	None	None	None	N
H/G	0.7274	likely_pathogenic	0.65	pathogenic	-1.084	Destabilizing	0.993	D	0.441	neutral	None	None	None	None	N
H/I	0.653	likely_pathogenic	0.5892	pathogenic	0.27	Stabilizing	0.999	D	0.562	neutral	None	None	None	None	N
H/K	0.5166	ambiguous	0.4538	ambiguous	-0.54	Destabilizing	0.971	D	0.36	neutral	None	None	None	None	N
H/L	0.3039	likely_benign	0.2761	benign	0.27	Stabilizing	0.997	D	0.545	neutral	N	0.491404002	None	None	N
H/M	0.8305	likely_pathogenic	0.7967	pathogenic	0.153	Stabilizing	1.0	D	0.483	neutral	None	None	None	None	N
H/N	0.2381	likely_benign	0.2144	benign	-0.6	Destabilizing	0.99	D	0.427	neutral	N	0.491538209	None	None	N
H/P	0.4082	ambiguous	0.3345	benign	-0.039	Destabilizing	0.999	D	0.469	neutral	D	0.532000751	None	None	N
H/Q	0.5164	ambiguous	0.4396	ambiguous	-0.385	Destabilizing	0.994	D	0.4	neutral	N	0.49136485	None	None	N
H/R	0.229	likely_benign	0.1894	benign	-0.99	Destabilizing	0.135	N	0.245	neutral	N	0.41634423	None	None	N
H/S	0.6085	likely_pathogenic	0.5361	ambiguous	-0.664	Destabilizing	0.993	D	0.389	neutral	None	None	None	None	N
H/T	0.6926	likely_pathogenic	0.6248	pathogenic	-0.466	Destabilizing	0.998	D	0.432	neutral	None	None	None	None	N
H/V	0.6556	likely_pathogenic	0.6034	pathogenic	-0.039	Destabilizing	0.998	D	0.567	neutral	None	None	None	None	N
H/W	0.6808	likely_pathogenic	0.6465	pathogenic	0.524	Stabilizing	1.0	D	0.559	neutral	None	None	None	None	N
H/Y	0.211	likely_benign	0.1933	benign	0.687	Stabilizing	0.997	D	0.442	neutral	D	0.524015986	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.