TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14881	44866;44867;44868	chr2:178624639;178624638;178624637	chr2:179489366;179489365;179489364
N2AB	13240	39943;39944;39945	chr2:178624639;178624638;178624637	chr2:179489366;179489365;179489364
N2A	12313	37162;37163;37164	chr2:178624639;178624638;178624637	chr2:179489366;179489365;179489364
N2B	5816	17671;17672;17673	chr2:178624639;178624638;178624637	chr2:179489366;179489365;179489364
Novex-1	5941	18046;18047;18048	chr2:178624639;178624638;178624637	chr2:179489366;179489365;179489364
Novex-2	6008	18247;18248;18249	chr2:178624639;178624638;178624637	chr2:179489366;179489365;179489364
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-100
• Domain position: 29
• Structural Position: 44
• Q(SASA): 0.2939
• 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	rs780650251	-0.366	0.919	N	0.651	0.334	0.492749560936	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	8.72E-05	None	0	0	None	0	None	0	0	0
A/V	rs780650251	-0.366	0.919	N	0.651	0.334	0.492749560936	gnomAD-4.0.0	6.37519E-06	None	None	None	None	N	None	0	6.87285E-05	None	0	0	None	0	0	2.86272E-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	0.8657	likely_pathogenic	0.8441	pathogenic	-0.78	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
A/D	0.9142	likely_pathogenic	0.8846	pathogenic	-0.943	Destabilizing	0.988	D	0.777	deleterious	D	0.724245643	None	None	N
A/E	0.8832	likely_pathogenic	0.8337	pathogenic	-1.045	Destabilizing	0.991	D	0.807	deleterious	None	None	None	None	N
A/F	0.9195	likely_pathogenic	0.8942	pathogenic	-1.021	Destabilizing	0.995	D	0.771	deleterious	None	None	None	None	N
A/G	0.4723	ambiguous	0.4262	ambiguous	-0.869	Destabilizing	0.958	D	0.615	neutral	D	0.55211498	None	None	N
A/H	0.9527	likely_pathogenic	0.9404	pathogenic	-0.986	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
A/I	0.8521	likely_pathogenic	0.7727	pathogenic	-0.428	Destabilizing	0.991	D	0.814	deleterious	None	None	None	None	N
A/K	0.9741	likely_pathogenic	0.9587	pathogenic	-1.141	Destabilizing	0.991	D	0.811	deleterious	None	None	None	None	N
A/L	0.7785	likely_pathogenic	0.7309	pathogenic	-0.428	Destabilizing	0.938	D	0.698	prob.neutral	None	None	None	None	N
A/M	0.8758	likely_pathogenic	0.8123	pathogenic	-0.331	Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
A/N	0.9057	likely_pathogenic	0.877	pathogenic	-0.721	Destabilizing	0.991	D	0.767	deleterious	None	None	None	None	N
A/P	0.9058	likely_pathogenic	0.8953	pathogenic	-0.48	Destabilizing	0.994	D	0.806	deleterious	N	0.473198857	None	None	N
A/Q	0.889	likely_pathogenic	0.8503	pathogenic	-0.968	Destabilizing	0.995	D	0.795	deleterious	None	None	None	None	N
A/R	0.9337	likely_pathogenic	0.9107	pathogenic	-0.667	Destabilizing	0.991	D	0.799	deleterious	None	None	None	None	N
A/S	0.2788	likely_benign	0.2268	benign	-0.98	Destabilizing	0.919	D	0.545	neutral	D	0.548198286	None	None	N
A/T	0.4788	ambiguous	0.3543	ambiguous	-0.999	Destabilizing	0.142	N	0.423	neutral	N	0.509808864	None	None	N
A/V	0.6077	likely_pathogenic	0.4804	ambiguous	-0.48	Destabilizing	0.919	D	0.651	neutral	N	0.507929475	None	None	N
A/W	0.9853	likely_pathogenic	0.9815	pathogenic	-1.25	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
A/Y	0.9547	likely_pathogenic	0.9438	pathogenic	-0.902	Destabilizing	1.0	D	0.764	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.