TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29158	87697;87698;87699	chr2:178557882;178557881;178557880	chr2:179422609;179422608;179422607
N2AB	27517	82774;82775;82776	chr2:178557882;178557881;178557880	chr2:179422609;179422608;179422607
N2A	26590	79993;79994;79995	chr2:178557882;178557881;178557880	chr2:179422609;179422608;179422607
N2B	20093	60502;60503;60504	chr2:178557882;178557881;178557880	chr2:179422609;179422608;179422607
Novex-1	20218	60877;60878;60879	chr2:178557882;178557881;178557880	chr2:179422609;179422608;179422607
Novex-2	20285	61078;61079;61080	chr2:178557882;178557881;178557880	chr2:179422609;179422608;179422607
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-100
• Domain position: 22
• Structural Position: 23
• Q(SASA): 0.547
• 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
K/Q	rs759043788	-0.671	0.036	N	0.373	0.112	0.15556083564	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.56E-05	None	0	None	0	0	0
K/Q	rs759043788	-0.671	0.036	N	0.373	0.112	0.15556083564	gnomAD-4.0.0	1.59127E-06	None	None	None	None	N	None	0	0	None	0	2.77269E-05	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
K/A	0.2471	likely_benign	0.2568	benign	-0.856	Destabilizing	0.25	N	0.439	neutral	None	None	None	None	N
K/C	0.3872	ambiguous	0.4102	ambiguous	-0.839	Destabilizing	0.992	D	0.666	neutral	None	None	None	None	N
K/D	0.5635	ambiguous	0.5901	pathogenic	0.169	Stabilizing	0.447	N	0.487	neutral	None	None	None	None	N
K/E	0.1751	likely_benign	0.1886	benign	0.319	Stabilizing	0.379	N	0.398	neutral	N	0.451043088	None	None	N
K/F	0.5821	likely_pathogenic	0.5831	pathogenic	-0.466	Destabilizing	0.85	D	0.644	neutral	None	None	None	None	N
K/G	0.3837	ambiguous	0.3889	ambiguous	-1.238	Destabilizing	0.617	D	0.529	neutral	None	None	None	None	N
K/H	0.1673	likely_benign	0.1737	benign	-1.397	Destabilizing	0.92	D	0.601	neutral	None	None	None	None	N
K/I	0.247	likely_benign	0.2635	benign	0.152	Stabilizing	0.681	D	0.623	neutral	N	0.515249282	None	None	N
K/L	0.2126	likely_benign	0.2247	benign	0.152	Stabilizing	0.447	N	0.539	neutral	None	None	None	None	N
K/M	0.1518	likely_benign	0.1576	benign	-0.051	Destabilizing	0.25	N	0.458	neutral	None	None	None	None	N
K/N	0.3049	likely_benign	0.3195	benign	-0.459	Destabilizing	0.036	N	0.383	neutral	N	0.472477153	None	None	N
K/P	0.9396	likely_pathogenic	0.9461	pathogenic	-0.155	Destabilizing	0.92	D	0.589	neutral	None	None	None	None	N
K/Q	0.0838	likely_benign	0.0888	benign	-0.48	Destabilizing	0.036	N	0.373	neutral	N	0.432804044	None	None	N
K/R	0.0714	likely_benign	0.0736	benign	-0.434	Destabilizing	0.004	N	0.407	neutral	N	0.475728102	None	None	N
K/S	0.2329	likely_benign	0.2487	benign	-1.274	Destabilizing	0.447	N	0.395	neutral	None	None	None	None	N
K/T	0.1066	likely_benign	0.1125	benign	-0.897	Destabilizing	0.004	N	0.407	neutral	N	0.434265482	None	None	N
K/V	0.2318	likely_benign	0.2512	benign	-0.155	Destabilizing	0.447	N	0.535	neutral	None	None	None	None	N
K/W	0.5941	likely_pathogenic	0.6071	pathogenic	-0.266	Destabilizing	0.992	D	0.707	prob.neutral	None	None	None	None	N
K/Y	0.4407	ambiguous	0.4419	ambiguous	0.02	Stabilizing	0.972	D	0.639	neutral	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.