TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22418	67477;67478;67479	chr2:178580035;178580034;178580033	chr2:179444762;179444761;179444760
N2AB	20777	62554;62555;62556	chr2:178580035;178580034;178580033	chr2:179444762;179444761;179444760
N2A	19850	59773;59774;59775	chr2:178580035;178580034;178580033	chr2:179444762;179444761;179444760
N2B	13353	40282;40283;40284	chr2:178580035;178580034;178580033	chr2:179444762;179444761;179444760
Novex-1	13478	40657;40658;40659	chr2:178580035;178580034;178580033	chr2:179444762;179444761;179444760
Novex-2	13545	40858;40859;40860	chr2:178580035;178580034;178580033	chr2:179444762;179444761;179444760
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-50
• Domain position: 65
• Structural Position: 97
• Q(SASA): 0.143
• 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
L/V	None	None	0.865	D	0.849	0.537	0.645408611234	gnomAD-4.0.0	6.84387E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99669E-07	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
L/A	0.9642	likely_pathogenic	0.9624	pathogenic	-2.681	Highly Destabilizing	0.944	D	0.828	deleterious	None	None	None	None	N
L/C	0.9513	likely_pathogenic	0.9495	pathogenic	-2.295	Highly Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
L/D	0.9993	likely_pathogenic	0.9991	pathogenic	-2.938	Highly Destabilizing	0.997	D	0.892	deleterious	None	None	None	None	N
L/E	0.9962	likely_pathogenic	0.9955	pathogenic	-2.818	Highly Destabilizing	0.997	D	0.877	deleterious	None	None	None	None	N
L/F	0.8658	likely_pathogenic	0.8546	pathogenic	-1.922	Destabilizing	0.085	N	0.657	neutral	D	0.659636455	None	None	N
L/G	0.9933	likely_pathogenic	0.9917	pathogenic	-3.143	Highly Destabilizing	0.992	D	0.881	deleterious	None	None	None	None	N
L/H	0.9943	likely_pathogenic	0.9929	pathogenic	-2.362	Highly Destabilizing	0.999	D	0.87	deleterious	None	None	None	None	N
L/I	0.3786	ambiguous	0.3253	benign	-1.386	Destabilizing	0.895	D	0.847	deleterious	None	None	None	None	N
L/K	0.9922	likely_pathogenic	0.9906	pathogenic	-2.09	Highly Destabilizing	0.992	D	0.873	deleterious	None	None	None	None	N
L/M	0.4081	ambiguous	0.4159	ambiguous	-1.274	Destabilizing	0.989	D	0.853	deleterious	D	0.614364348	None	None	N
L/N	0.996	likely_pathogenic	0.9953	pathogenic	-2.251	Highly Destabilizing	0.997	D	0.889	deleterious	None	None	None	None	N
L/P	0.9929	likely_pathogenic	0.9915	pathogenic	-1.795	Destabilizing	0.997	D	0.887	deleterious	None	None	None	None	N
L/Q	0.9867	likely_pathogenic	0.9848	pathogenic	-2.324	Highly Destabilizing	0.999	D	0.881	deleterious	None	None	None	None	N
L/R	0.9852	likely_pathogenic	0.9824	pathogenic	-1.5	Destabilizing	0.992	D	0.879	deleterious	None	None	None	None	N
L/S	0.9953	likely_pathogenic	0.9945	pathogenic	-2.956	Highly Destabilizing	0.989	D	0.862	deleterious	D	0.685981783	None	None	N
L/T	0.9495	likely_pathogenic	0.9416	pathogenic	-2.698	Highly Destabilizing	0.992	D	0.858	deleterious	None	None	None	None	N
L/V	0.4674	ambiguous	0.4167	ambiguous	-1.795	Destabilizing	0.865	D	0.849	deleterious	D	0.60603678	None	None	N
L/W	0.9855	likely_pathogenic	0.982	pathogenic	-2.146	Highly Destabilizing	0.999	D	0.846	deleterious	D	0.685981783	None	None	N
L/Y	0.9907	likely_pathogenic	0.9889	pathogenic	-1.929	Destabilizing	0.968	D	0.852	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.