TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29146	87661;87662;87663	chr2:178557918;178557917;178557916	chr2:179422645;179422644;179422643
N2AB	27505	82738;82739;82740	chr2:178557918;178557917;178557916	chr2:179422645;179422644;179422643
N2A	26578	79957;79958;79959	chr2:178557918;178557917;178557916	chr2:179422645;179422644;179422643
N2B	20081	60466;60467;60468	chr2:178557918;178557917;178557916	chr2:179422645;179422644;179422643
Novex-1	20206	60841;60842;60843	chr2:178557918;178557917;178557916	chr2:179422645;179422644;179422643
Novex-2	20273	61042;61043;61044	chr2:178557918;178557917;178557916	chr2:179422645;179422644;179422643
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: 10
• Structural Position: 11
• Q(SASA): 0.3725
• Predicted PPI site: I

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	rs794729520	None	0.317	N	0.626	0.113	0.650379344195	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
V/F	rs794729520	None	0.317	N	0.626	0.113	0.650379344195	gnomAD-4.0.0	1.31428E-05	None	None	None	None	I	None	4.82532E-05	0	None	0	0	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
V/A	0.1002	likely_benign	0.1024	benign	-0.76	Destabilizing	None	N	0.169	neutral	N	0.459721287	None	None	I
V/C	0.4639	ambiguous	0.4701	ambiguous	-0.724	Destabilizing	0.824	D	0.581	neutral	None	None	None	None	I
V/D	0.168	likely_benign	0.1792	benign	-0.462	Destabilizing	0.062	N	0.546	neutral	N	0.438884655	None	None	I
V/E	0.13	likely_benign	0.136	benign	-0.53	Destabilizing	0.001	N	0.355	neutral	None	None	None	None	I
V/F	0.116	likely_benign	0.1144	benign	-0.69	Destabilizing	0.317	N	0.626	neutral	N	0.495604729	None	None	I
V/G	0.1437	likely_benign	0.154	benign	-0.97	Destabilizing	0.062	N	0.55	neutral	N	0.46545518	None	None	I
V/H	0.271	likely_benign	0.2787	benign	-0.481	Destabilizing	0.935	D	0.589	neutral	None	None	None	None	I
V/I	0.0684	likely_benign	0.0685	benign	-0.333	Destabilizing	None	N	0.207	neutral	N	0.465628539	None	None	I
V/K	0.1682	likely_benign	0.1667	benign	-0.753	Destabilizing	0.149	N	0.541	neutral	None	None	None	None	I
V/L	0.1063	likely_benign	0.1067	benign	-0.333	Destabilizing	0.027	N	0.4	neutral	N	0.448832289	None	None	I
V/M	0.0937	likely_benign	0.0941	benign	-0.394	Destabilizing	0.38	N	0.545	neutral	None	None	None	None	I
V/N	0.123	likely_benign	0.1304	benign	-0.512	Destabilizing	0.38	N	0.626	neutral	None	None	None	None	I
V/P	0.6286	likely_pathogenic	0.6904	pathogenic	-0.439	Destabilizing	0.38	N	0.635	neutral	None	None	None	None	I
V/Q	0.1563	likely_benign	0.1554	benign	-0.706	Destabilizing	0.38	N	0.639	neutral	None	None	None	None	I
V/R	0.1732	likely_benign	0.1728	benign	-0.236	Destabilizing	0.38	N	0.633	neutral	None	None	None	None	I
V/S	0.1087	likely_benign	0.1129	benign	-0.935	Destabilizing	0.081	N	0.537	neutral	None	None	None	None	I
V/T	0.098	likely_benign	0.0997	benign	-0.896	Destabilizing	0.001	N	0.217	neutral	None	None	None	None	I
V/W	0.6125	likely_pathogenic	0.6288	pathogenic	-0.806	Destabilizing	0.935	D	0.614	neutral	None	None	None	None	I
V/Y	0.3046	likely_benign	0.3176	benign	-0.521	Destabilizing	0.555	D	0.621	neutral	None	None	None	None	I

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.