TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15741	47446;47447;47448	chr2:178618237;178618236;178618235	chr2:179482964;179482963;179482962
N2AB	14100	42523;42524;42525	chr2:178618237;178618236;178618235	chr2:179482964;179482963;179482962
N2A	13173	39742;39743;39744	chr2:178618237;178618236;178618235	chr2:179482964;179482963;179482962
N2B	6676	20251;20252;20253	chr2:178618237;178618236;178618235	chr2:179482964;179482963;179482962
Novex-1	6801	20626;20627;20628	chr2:178618237;178618236;178618235	chr2:179482964;179482963;179482962
Novex-2	6868	20827;20828;20829	chr2:178618237;178618236;178618235	chr2:179482964;179482963;179482962
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-1
• Domain position: 85
• Structural Position: 118
• Q(SASA): 0.1416
• 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
G/A	rs779498799	-0.691	1.0	D	0.691	0.635	0.461323234107	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
G/A	rs779498799	-0.691	1.0	D	0.691	0.635	0.461323234107	gnomAD-4.0.0	6.3728E-06	None	None	None	None	N	None	0	0	None	0	2.77701E-05	None	0	0	0	4.30034E-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
G/A	0.5415	ambiguous	0.5917	pathogenic	-0.804	Destabilizing	1.0	D	0.691	prob.neutral	D	0.740767103	None	None	N
G/C	0.9114	likely_pathogenic	0.911	pathogenic	-1.087	Destabilizing	1.0	D	0.85	deleterious	D	0.777414965	None	None	N
G/D	0.9751	likely_pathogenic	0.9784	pathogenic	-1.326	Destabilizing	1.0	D	0.879	deleterious	D	0.742028193	None	None	N
G/E	0.9855	likely_pathogenic	0.9875	pathogenic	-1.432	Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
G/F	0.9962	likely_pathogenic	0.9966	pathogenic	-1.262	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
G/H	0.9918	likely_pathogenic	0.9921	pathogenic	-1.137	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
G/I	0.9916	likely_pathogenic	0.993	pathogenic	-0.647	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
G/K	0.9958	likely_pathogenic	0.9958	pathogenic	-1.217	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
G/L	0.9884	likely_pathogenic	0.9899	pathogenic	-0.647	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
G/M	0.9905	likely_pathogenic	0.9922	pathogenic	-0.553	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
G/N	0.9714	likely_pathogenic	0.9756	pathogenic	-0.899	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
G/P	0.9982	likely_pathogenic	0.9981	pathogenic	-0.663	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
G/Q	0.9871	likely_pathogenic	0.9884	pathogenic	-1.202	Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
G/R	0.987	likely_pathogenic	0.9868	pathogenic	-0.78	Destabilizing	1.0	D	0.921	deleterious	D	0.740157926	None	None	N
G/S	0.2979	likely_benign	0.3393	benign	-1.1	Destabilizing	1.0	D	0.807	deleterious	N	0.492530074	None	None	N
G/T	0.8356	likely_pathogenic	0.8662	pathogenic	-1.146	Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
G/V	0.9721	likely_pathogenic	0.9764	pathogenic	-0.663	Destabilizing	1.0	D	0.903	deleterious	D	0.776883985	None	None	N
G/W	0.9916	likely_pathogenic	0.9917	pathogenic	-1.459	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
G/Y	0.995	likely_pathogenic	0.9951	pathogenic	-1.113	Destabilizing	1.0	D	0.875	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.