TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29120	87583;87584;87585	chr2:178557996;178557995;178557994	chr2:179422723;179422722;179422721
N2AB	27479	82660;82661;82662	chr2:178557996;178557995;178557994	chr2:179422723;179422722;179422721
N2A	26552	79879;79880;79881	chr2:178557996;178557995;178557994	chr2:179422723;179422722;179422721
N2B	20055	60388;60389;60390	chr2:178557996;178557995;178557994	chr2:179422723;179422722;179422721
Novex-1	20180	60763;60764;60765	chr2:178557996;178557995;178557994	chr2:179422723;179422722;179422721
Novex-2	20247	60964;60965;60966	chr2:178557996;178557995;178557994	chr2:179422723;179422722;179422721
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-145
• Domain position: 76
• Structural Position: 159
• Q(SASA): 0.2612
• 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
A/V	None	None	0.505	N	0.472	0.24	0.487772906946	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
A/C	0.3188	likely_benign	0.3081	benign	-0.859	Destabilizing	0.973	D	0.539	neutral	None	None	None	None	N
A/D	0.3123	likely_benign	0.3102	benign	-1.164	Destabilizing	0.338	N	0.655	neutral	N	0.485324312	None	None	N
A/E	0.231	likely_benign	0.2254	benign	-1.304	Destabilizing	0.404	N	0.495	neutral	None	None	None	None	N
A/F	0.2784	likely_benign	0.2561	benign	-1.338	Destabilizing	0.906	D	0.7	prob.neutral	None	None	None	None	N
A/G	0.1448	likely_benign	0.1483	benign	-0.785	Destabilizing	0.174	N	0.429	neutral	N	0.485671029	None	None	N
A/H	0.4014	ambiguous	0.374	ambiguous	-0.872	Destabilizing	0.973	D	0.693	prob.neutral	None	None	None	None	N
A/I	0.1896	likely_benign	0.1698	benign	-0.629	Destabilizing	0.826	D	0.577	neutral	None	None	None	None	N
A/K	0.4276	ambiguous	0.4139	ambiguous	-0.886	Destabilizing	0.404	N	0.527	neutral	None	None	None	None	N
A/L	0.1603	likely_benign	0.1499	benign	-0.629	Destabilizing	0.575	D	0.495	neutral	None	None	None	None	N
A/M	0.1745	likely_benign	0.1591	benign	-0.375	Destabilizing	0.991	D	0.588	neutral	None	None	None	None	N
A/N	0.2183	likely_benign	0.2016	benign	-0.585	Destabilizing	0.018	N	0.46	neutral	None	None	None	None	N
A/P	0.9009	likely_pathogenic	0.9039	pathogenic	-0.616	Destabilizing	0.879	D	0.565	neutral	N	0.504699507	None	None	N
A/Q	0.2717	likely_benign	0.2648	benign	-0.941	Destabilizing	0.826	D	0.58	neutral	None	None	None	None	N
A/R	0.3978	ambiguous	0.3981	ambiguous	-0.379	Destabilizing	0.826	D	0.537	neutral	None	None	None	None	N
A/S	0.0775	likely_benign	0.0769	benign	-0.774	Destabilizing	0.001	N	0.149	neutral	N	0.388584412	None	None	N
A/T	0.0702	likely_benign	0.0661	benign	-0.848	Destabilizing	0.338	N	0.416	neutral	N	0.410285049	None	None	N
A/V	0.1091	likely_benign	0.1019	benign	-0.616	Destabilizing	0.505	D	0.472	neutral	N	0.466565193	None	None	N
A/W	0.6813	likely_pathogenic	0.6664	pathogenic	-1.475	Destabilizing	0.991	D	0.761	deleterious	None	None	None	None	N
A/Y	0.3856	ambiguous	0.3612	ambiguous	-1.122	Destabilizing	0.906	D	0.702	prob.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.