TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23101	69526;69527;69528	chr2:178577034;178577033;178577032	chr2:179441761;179441760;179441759
N2AB	21460	64603;64604;64605	chr2:178577034;178577033;178577032	chr2:179441761;179441760;179441759
N2A	20533	61822;61823;61824	chr2:178577034;178577033;178577032	chr2:179441761;179441760;179441759
N2B	14036	42331;42332;42333	chr2:178577034;178577033;178577032	chr2:179441761;179441760;179441759
Novex-1	14161	42706;42707;42708	chr2:178577034;178577033;178577032	chr2:179441761;179441760;179441759
Novex-2	14228	42907;42908;42909	chr2:178577034;178577033;178577032	chr2:179441761;179441760;179441759
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-55
• Domain position: 62
• Structural Position: 93
• Q(SASA): 0.1219
• 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/V	None	None	None	N	0.293	0.086	0.190952846119	gnomAD-4.0.0	1.59188E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85963E-06	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
A/C	0.463	ambiguous	0.4714	ambiguous	-1.043	Destabilizing	0.909	D	0.714	prob.delet.	None	None	None	None	N
A/D	0.9497	likely_pathogenic	0.9588	pathogenic	-2.07	Highly Destabilizing	0.726	D	0.842	deleterious	None	None	None	None	N
A/E	0.895	likely_pathogenic	0.9112	pathogenic	-1.939	Destabilizing	0.667	D	0.817	deleterious	N	0.4721028	None	None	N
A/F	0.6472	likely_pathogenic	0.6898	pathogenic	-0.864	Destabilizing	0.567	D	0.839	deleterious	None	None	None	None	N
A/G	0.4324	ambiguous	0.4221	ambiguous	-1.548	Destabilizing	0.364	N	0.678	prob.neutral	N	0.486991051	None	None	N
A/H	0.9373	likely_pathogenic	0.9489	pathogenic	-1.974	Destabilizing	0.968	D	0.832	deleterious	None	None	None	None	N
A/I	0.1636	likely_benign	0.169	benign	0.001	Stabilizing	0.06	N	0.74	deleterious	None	None	None	None	N
A/K	0.9569	likely_pathogenic	0.9702	pathogenic	-1.489	Destabilizing	0.726	D	0.809	deleterious	None	None	None	None	N
A/L	0.2305	likely_benign	0.2605	benign	0.001	Stabilizing	0.072	N	0.735	prob.delet.	None	None	None	None	N
A/M	0.3171	likely_benign	0.315	benign	-0.028	Destabilizing	0.567	D	0.793	deleterious	None	None	None	None	N
A/N	0.8565	likely_pathogenic	0.8691	pathogenic	-1.508	Destabilizing	0.89	D	0.831	deleterious	None	None	None	None	N
A/P	0.8216	likely_pathogenic	0.8658	pathogenic	-0.327	Destabilizing	0.859	D	0.808	deleterious	N	0.475723651	None	None	N
A/Q	0.8695	likely_pathogenic	0.8906	pathogenic	-1.426	Destabilizing	0.89	D	0.787	deleterious	None	None	None	None	N
A/R	0.9282	likely_pathogenic	0.9511	pathogenic	-1.411	Destabilizing	0.726	D	0.802	deleterious	None	None	None	None	N
A/S	0.236	likely_benign	0.2261	benign	-1.902	Destabilizing	0.22	N	0.672	neutral	N	0.511534187	None	None	N
A/T	0.1316	likely_benign	0.121	benign	-1.647	Destabilizing	0.124	N	0.678	prob.neutral	N	0.499317038	None	None	N
A/V	0.0682	likely_benign	0.0712	benign	-0.327	Destabilizing	None	N	0.293	neutral	N	0.339733594	None	None	N
A/W	0.9622	likely_pathogenic	0.971	pathogenic	-1.536	Destabilizing	0.968	D	0.831	deleterious	None	None	None	None	N
A/Y	0.8828	likely_pathogenic	0.907	pathogenic	-1.002	Destabilizing	0.726	D	0.833	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.