TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17783	53572;53573;53574	chr2:178607255;178607254;178607253	chr2:179471982;179471981;179471980
N2AB	16142	48649;48650;48651	chr2:178607255;178607254;178607253	chr2:179471982;179471981;179471980
N2A	15215	45868;45869;45870	chr2:178607255;178607254;178607253	chr2:179471982;179471981;179471980
N2B	8718	26377;26378;26379	chr2:178607255;178607254;178607253	chr2:179471982;179471981;179471980
Novex-1	8843	26752;26753;26754	chr2:178607255;178607254;178607253	chr2:179471982;179471981;179471980
Novex-2	8910	26953;26954;26955	chr2:178607255;178607254;178607253	chr2:179471982;179471981;179471980
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-17
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.1182
• 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/P	rs777712545	-1.89	1.0	D	0.879	0.821	0.779797818376	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.62E-05	None	0	None	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
L/A	0.9868	likely_pathogenic	0.9879	pathogenic	-2.712	Highly Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	N
L/C	0.9765	likely_pathogenic	0.9767	pathogenic	-1.787	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
L/D	0.9996	likely_pathogenic	0.9997	pathogenic	-3.472	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
L/E	0.9978	likely_pathogenic	0.9983	pathogenic	-3.158	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/F	0.8288	likely_pathogenic	0.8781	pathogenic	-1.717	Destabilizing	1.0	D	0.707	prob.neutral	D	0.523849849	None	None	N
L/G	0.9974	likely_pathogenic	0.9979	pathogenic	-3.274	Highly Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
L/H	0.9966	likely_pathogenic	0.9975	pathogenic	-3.078	Highly Destabilizing	1.0	D	0.838	deleterious	D	0.543221552	None	None	N
L/I	0.2486	likely_benign	0.2503	benign	-0.996	Destabilizing	0.999	D	0.563	neutral	N	0.479190961	None	None	N
L/K	0.9966	likely_pathogenic	0.9971	pathogenic	-2.184	Highly Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
L/M	0.5269	ambiguous	0.5777	pathogenic	-1.181	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
L/N	0.9986	likely_pathogenic	0.9986	pathogenic	-2.969	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
L/P	0.9976	likely_pathogenic	0.9979	pathogenic	-1.563	Destabilizing	1.0	D	0.879	deleterious	D	0.543221552	None	None	N
L/Q	0.9933	likely_pathogenic	0.9952	pathogenic	-2.572	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
L/R	0.9934	likely_pathogenic	0.9946	pathogenic	-2.345	Highly Destabilizing	1.0	D	0.843	deleterious	D	0.543221552	None	None	N
L/S	0.9986	likely_pathogenic	0.9988	pathogenic	-3.372	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
L/T	0.9917	likely_pathogenic	0.992	pathogenic	-2.901	Highly Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
L/V	0.4165	ambiguous	0.3951	ambiguous	-1.563	Destabilizing	0.999	D	0.588	neutral	N	0.501496125	None	None	N
L/W	0.9855	likely_pathogenic	0.9893	pathogenic	-2.051	Highly Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
L/Y	0.9907	likely_pathogenic	0.9928	pathogenic	-1.92	Destabilizing	1.0	D	0.757	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.