TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15137	45634;45635;45636	chr2:178621309;178621308;178621307	chr2:179486036;179486035;179486034
N2AB	13496	40711;40712;40713	chr2:178621309;178621308;178621307	chr2:179486036;179486035;179486034
N2A	12569	37930;37931;37932	chr2:178621309;178621308;178621307	chr2:179486036;179486035;179486034
N2B	6072	18439;18440;18441	chr2:178621309;178621308;178621307	chr2:179486036;179486035;179486034
Novex-1	6197	18814;18815;18816	chr2:178621309;178621308;178621307	chr2:179486036;179486035;179486034
Novex-2	6264	19015;19016;19017	chr2:178621309;178621308;178621307	chr2:179486036;179486035;179486034
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-103
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.124
• 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
A/D	rs1305459337	-2.052	1.0	D	0.84	0.486	0.651316673006	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
A/D	rs1305459337	-2.052	1.0	D	0.84	0.486	0.651316673006	gnomAD-4.0.0	1.59519E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43526E-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
A/C	0.8404	likely_pathogenic	0.8791	pathogenic	-1.0	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
A/D	0.993	likely_pathogenic	0.9931	pathogenic	-2.168	Highly Destabilizing	1.0	D	0.84	deleterious	D	0.701160056	None	None	N
A/E	0.985	likely_pathogenic	0.9866	pathogenic	-1.976	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
A/F	0.9629	likely_pathogenic	0.9761	pathogenic	-0.811	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
A/G	0.3082	likely_benign	0.311	benign	-1.67	Destabilizing	1.0	D	0.584	neutral	D	0.612325246	None	None	N
A/H	0.9943	likely_pathogenic	0.9955	pathogenic	-1.957	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
A/I	0.7536	likely_pathogenic	0.8376	pathogenic	0.059	Stabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
A/K	0.9947	likely_pathogenic	0.995	pathogenic	-1.478	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
A/L	0.7449	likely_pathogenic	0.8197	pathogenic	0.059	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
A/M	0.8257	likely_pathogenic	0.8858	pathogenic	-0.002	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
A/N	0.9813	likely_pathogenic	0.9854	pathogenic	-1.664	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
A/P	0.9814	likely_pathogenic	0.9831	pathogenic	-0.317	Destabilizing	1.0	D	0.846	deleterious	D	0.664526904	None	None	N
A/Q	0.979	likely_pathogenic	0.9822	pathogenic	-1.505	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
A/R	0.9873	likely_pathogenic	0.9871	pathogenic	-1.471	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
A/S	0.441	ambiguous	0.4755	ambiguous	-2.101	Highly Destabilizing	1.0	D	0.599	neutral	D	0.624645815	None	None	N
A/T	0.4802	ambiguous	0.5589	ambiguous	-1.776	Destabilizing	1.0	D	0.696	prob.neutral	D	0.566405255	None	None	N
A/V	0.3939	ambiguous	0.4852	ambiguous	-0.317	Destabilizing	1.0	D	0.615	neutral	N	0.440347153	None	None	N
A/W	0.9975	likely_pathogenic	0.9981	pathogenic	-1.513	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
A/Y	0.9875	likely_pathogenic	0.9915	pathogenic	-0.947	Destabilizing	1.0	D	0.871	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.