TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9577	28954;28955;28956	chr2:178709590;178709589;178709588	chr2:179574317;179574316;179574315
N2AB	9260	28003;28004;28005	chr2:178709590;178709589;178709588	chr2:179574317;179574316;179574315
N2A	8333	25222;25223;25224	chr2:178709590;178709589;178709588	chr2:179574317;179574316;179574315
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-81
• Domain position: 85
• Structural Position: 169
• Q(SASA): 0.2166
• Predicted PPI site: I

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
C/G	rs1476712853	-1.693	0.669	None	0.735	0.421	0.803902362773	gnomAD-2.1.1	3.18E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	2.87687E-04	0	0
C/G	rs1476712853	-1.693	0.669	None	0.735	0.421	0.803902362773	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	9.41E-05	0	0	0	0
C/G	rs1476712853	-1.693	0.669	None	0.735	0.421	0.803902362773	gnomAD-4.0.0	2.02974E-06	None	None	None	None	I	None	0	0	None	0	0	None	9.17263E-05	0	1.2049E-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
C/A	0.5117	ambiguous	0.5	ambiguous	-1.842	Destabilizing	0.525	D	0.587	neutral	None	None	None	None	I
C/D	0.9057	likely_pathogenic	0.911	pathogenic	-0.192	Destabilizing	0.949	D	0.776	deleterious	None	None	None	None	I
C/E	0.9587	likely_pathogenic	0.9618	pathogenic	-0.064	Destabilizing	0.949	D	0.779	deleterious	None	None	None	None	I
C/F	0.4408	ambiguous	0.4867	ambiguous	-1.157	Destabilizing	0.028	N	0.599	neutral	None	None	None	None	I
C/G	0.3418	ambiguous	0.3282	benign	-2.165	Highly Destabilizing	0.669	D	0.735	prob.delet.	None	None	None	None	I
C/H	0.8398	likely_pathogenic	0.8608	pathogenic	-1.981	Destabilizing	0.998	D	0.777	deleterious	None	None	None	None	I
C/I	0.7987	likely_pathogenic	0.795	pathogenic	-0.998	Destabilizing	0.842	D	0.721	prob.delet.	None	None	None	None	I
C/K	0.9812	likely_pathogenic	0.9835	pathogenic	-0.836	Destabilizing	0.949	D	0.779	deleterious	None	None	None	None	I
C/L	0.6967	likely_pathogenic	0.7104	pathogenic	-0.998	Destabilizing	0.728	D	0.64	neutral	None	None	None	None	I
C/M	0.8311	likely_pathogenic	0.8315	pathogenic	0.023	Stabilizing	0.991	D	0.711	prob.delet.	None	None	None	None	I
C/N	0.7802	likely_pathogenic	0.7879	pathogenic	-0.96	Destabilizing	0.949	D	0.786	deleterious	None	None	None	None	I
C/P	0.997	likely_pathogenic	0.9974	pathogenic	-1.255	Destabilizing	0.974	D	0.802	deleterious	None	None	None	None	I
C/Q	0.8912	likely_pathogenic	0.9069	pathogenic	-0.779	Destabilizing	0.974	D	0.795	deleterious	None	None	None	None	I
C/R	0.8884	likely_pathogenic	0.8992	pathogenic	-0.758	Destabilizing	0.934	D	0.803	deleterious	None	None	None	None	I
C/S	0.3275	likely_benign	0.3134	benign	-1.539	Destabilizing	0.051	N	0.509	neutral	None	None	None	None	I
C/T	0.5878	likely_pathogenic	0.5565	ambiguous	-1.213	Destabilizing	0.728	D	0.655	neutral	None	None	None	None	I
C/V	0.6688	likely_pathogenic	0.6656	pathogenic	-1.255	Destabilizing	0.842	D	0.661	neutral	None	None	None	None	I
C/W	0.8456	likely_pathogenic	0.8567	pathogenic	-1.121	Destabilizing	0.997	D	0.725	prob.delet.	None	None	None	None	I
C/Y	0.6282	likely_pathogenic	0.6693	pathogenic	-1.124	Destabilizing	0.876	D	0.738	prob.delet.	None	None	None	None	I

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.