TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18514	55765;55766;55767	chr2:178601457;178601456;178601455	chr2:179466184;179466183;179466182
N2AB	16873	50842;50843;50844	chr2:178601457;178601456;178601455	chr2:179466184;179466183;179466182
N2A	15946	48061;48062;48063	chr2:178601457;178601456;178601455	chr2:179466184;179466183;179466182
N2B	9449	28570;28571;28572	chr2:178601457;178601456;178601455	chr2:179466184;179466183;179466182
Novex-1	9574	28945;28946;28947	chr2:178601457;178601456;178601455	chr2:179466184;179466183;179466182
Novex-2	9641	29146;29147;29148	chr2:178601457;178601456;178601455	chr2:179466184;179466183;179466182
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-22
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.1135
• 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
Y/C	rs764002054	None	1.0	D	0.881	0.913	0.889664998482	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
Y/C	rs764002054	None	1.0	D	0.881	0.913	0.889664998482	gnomAD-4.0.0	6.5799E-06	None	None	None	None	N	None	2.41453E-05	0	None	0	0	None	0	0	0	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
Y/A	0.9971	likely_pathogenic	0.9978	pathogenic	-3.215	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
Y/C	0.9391	likely_pathogenic	0.9513	pathogenic	-2.119	Highly Destabilizing	1.0	D	0.881	deleterious	D	0.647458554	None	None	N
Y/D	0.9975	likely_pathogenic	0.998	pathogenic	-3.445	Highly Destabilizing	1.0	D	0.917	deleterious	D	0.647862162	None	None	N
Y/E	0.9993	likely_pathogenic	0.9994	pathogenic	-3.223	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
Y/F	0.1947	likely_benign	0.1672	benign	-1.249	Destabilizing	0.999	D	0.635	neutral	D	0.559207421	None	None	N
Y/G	0.9918	likely_pathogenic	0.9936	pathogenic	-3.654	Highly Destabilizing	1.0	D	0.929	deleterious	None	None	None	None	N
Y/H	0.9821	likely_pathogenic	0.9829	pathogenic	-2.336	Highly Destabilizing	1.0	D	0.796	deleterious	D	0.647458554	None	None	N
Y/I	0.9768	likely_pathogenic	0.9802	pathogenic	-1.748	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
Y/K	0.9987	likely_pathogenic	0.999	pathogenic	-2.281	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
Y/L	0.9525	likely_pathogenic	0.963	pathogenic	-1.748	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
Y/M	0.9829	likely_pathogenic	0.9858	pathogenic	-1.629	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
Y/N	0.9826	likely_pathogenic	0.9854	pathogenic	-3.094	Highly Destabilizing	1.0	D	0.897	deleterious	D	0.647862162	None	None	N
Y/P	0.9991	likely_pathogenic	0.9994	pathogenic	-2.254	Highly Destabilizing	1.0	D	0.944	deleterious	None	None	None	None	N
Y/Q	0.9986	likely_pathogenic	0.9989	pathogenic	-2.81	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
Y/R	0.9956	likely_pathogenic	0.9964	pathogenic	-2.094	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
Y/S	0.9918	likely_pathogenic	0.9936	pathogenic	-3.503	Highly Destabilizing	1.0	D	0.907	deleterious	D	0.622324051	None	None	N
Y/T	0.9962	likely_pathogenic	0.997	pathogenic	-3.149	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
Y/V	0.9649	likely_pathogenic	0.9713	pathogenic	-2.254	Highly Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
Y/W	0.7899	likely_pathogenic	0.7884	pathogenic	-0.505	Destabilizing	1.0	D	0.787	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.