TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7914	23965;23966;23967	chr2:178719752;178719751;178719750	chr2:179584479;179584478;179584477
N2AB	7597	23014;23015;23016	chr2:178719752;178719751;178719750	chr2:179584479;179584478;179584477
N2A	6670	20233;20234;20235	chr2:178719752;178719751;178719750	chr2:179584479;179584478;179584477
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: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-64
• Domain position: 26
• Structural Position: 40
• Q(SASA): 0.4045
• 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
G/E	None	None	1.0	D	0.804	0.637	0.70494342197	gnomAD-4.0.0	4.80129E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.25001E-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
G/A	0.7548	likely_pathogenic	0.7657	pathogenic	-0.376	Destabilizing	1.0	D	0.78	deleterious	D	0.577626996	None	None	I
G/C	0.9812	likely_pathogenic	0.9854	pathogenic	-0.823	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
G/D	0.986	likely_pathogenic	0.99	pathogenic	-0.78	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
G/E	0.9918	likely_pathogenic	0.9941	pathogenic	-0.916	Destabilizing	1.0	D	0.804	deleterious	D	0.605790358	None	None	I
G/F	0.9979	likely_pathogenic	0.9984	pathogenic	-0.965	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	I
G/H	0.9978	likely_pathogenic	0.9983	pathogenic	-0.795	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
G/I	0.9939	likely_pathogenic	0.9956	pathogenic	-0.338	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
G/K	0.9971	likely_pathogenic	0.9978	pathogenic	-1.077	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
G/L	0.9949	likely_pathogenic	0.9962	pathogenic	-0.338	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
G/M	0.9971	likely_pathogenic	0.9977	pathogenic	-0.369	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
G/N	0.9924	likely_pathogenic	0.9933	pathogenic	-0.658	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	I
G/P	0.9977	likely_pathogenic	0.9984	pathogenic	-0.313	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	I
G/Q	0.995	likely_pathogenic	0.9958	pathogenic	-0.917	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
G/R	0.9898	likely_pathogenic	0.9922	pathogenic	-0.64	Destabilizing	1.0	D	0.807	deleterious	D	0.621727562	None	None	I
G/S	0.8312	likely_pathogenic	0.8339	pathogenic	-0.81	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
G/T	0.9769	likely_pathogenic	0.9799	pathogenic	-0.874	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
G/V	0.9828	likely_pathogenic	0.9872	pathogenic	-0.313	Destabilizing	1.0	D	0.77	deleterious	D	0.641461557	None	None	I
G/W	0.9956	likely_pathogenic	0.9967	pathogenic	-1.202	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	I
G/Y	0.9968	likely_pathogenic	0.9976	pathogenic	-0.83	Destabilizing	1.0	D	0.757	deleterious	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.