TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29192	87799;87800;87801	chr2:178557780;178557779;178557778	chr2:179422507;179422506;179422505
N2AB	27551	82876;82877;82878	chr2:178557780;178557779;178557778	chr2:179422507;179422506;179422505
N2A	26624	80095;80096;80097	chr2:178557780;178557779;178557778	chr2:179422507;179422506;179422505
N2B	20127	60604;60605;60606	chr2:178557780;178557779;178557778	chr2:179422507;179422506;179422505
Novex-1	20252	60979;60980;60981	chr2:178557780;178557779;178557778	chr2:179422507;179422506;179422505
Novex-2	20319	61180;61181;61182	chr2:178557780;178557779;178557778	chr2:179422507;179422506;179422505
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-100
• Domain position: 56
• Structural Position: 77
• Q(SASA): 0.137
• 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
V/F	None	None	0.83	N	0.801	0.289	0.645427016598	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
V/A	0.3701	ambiguous	0.3716	ambiguous	-1.902	Destabilizing	0.581	D	0.506	neutral	N	0.519324164	None	None	N
V/C	0.8728	likely_pathogenic	0.864	pathogenic	-1.548	Destabilizing	0.993	D	0.779	deleterious	None	None	None	None	N
V/D	0.9713	likely_pathogenic	0.9722	pathogenic	-1.858	Destabilizing	0.908	D	0.865	deleterious	N	0.475595066	None	None	N
V/E	0.931	likely_pathogenic	0.9285	pathogenic	-1.743	Destabilizing	0.929	D	0.798	deleterious	None	None	None	None	N
V/F	0.6702	likely_pathogenic	0.6623	pathogenic	-1.257	Destabilizing	0.83	D	0.801	deleterious	N	0.479584765	None	None	N
V/G	0.7201	likely_pathogenic	0.7131	pathogenic	-2.356	Highly Destabilizing	0.908	D	0.814	deleterious	N	0.520169526	None	None	N
V/H	0.9709	likely_pathogenic	0.9682	pathogenic	-1.93	Destabilizing	0.993	D	0.874	deleterious	None	None	None	None	N
V/I	0.0986	likely_benign	0.114	benign	-0.693	Destabilizing	0.004	N	0.369	neutral	N	0.487830608	None	None	N
V/K	0.9517	likely_pathogenic	0.9484	pathogenic	-1.551	Destabilizing	0.929	D	0.812	deleterious	None	None	None	None	N
V/L	0.441	ambiguous	0.5166	ambiguous	-0.693	Destabilizing	0.09	N	0.443	neutral	N	0.476016104	None	None	N
V/M	0.3322	likely_benign	0.364	ambiguous	-0.68	Destabilizing	0.866	D	0.742	deleterious	None	None	None	None	N
V/N	0.8533	likely_pathogenic	0.8611	pathogenic	-1.577	Destabilizing	0.976	D	0.879	deleterious	None	None	None	None	N
V/P	0.9554	likely_pathogenic	0.9665	pathogenic	-1.063	Destabilizing	0.976	D	0.857	deleterious	None	None	None	None	N
V/Q	0.8972	likely_pathogenic	0.8843	pathogenic	-1.583	Destabilizing	0.976	D	0.861	deleterious	None	None	None	None	N
V/R	0.9332	likely_pathogenic	0.93	pathogenic	-1.206	Destabilizing	0.929	D	0.877	deleterious	None	None	None	None	N
V/S	0.6215	likely_pathogenic	0.6004	pathogenic	-2.252	Highly Destabilizing	0.929	D	0.779	deleterious	None	None	None	None	N
V/T	0.4156	ambiguous	0.411	ambiguous	-2.0	Highly Destabilizing	0.648	D	0.635	neutral	None	None	None	None	N
V/W	0.9906	likely_pathogenic	0.9893	pathogenic	-1.575	Destabilizing	0.993	D	0.841	deleterious	None	None	None	None	N
V/Y	0.9554	likely_pathogenic	0.9557	pathogenic	-1.244	Destabilizing	0.929	D	0.823	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.