TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29122	87589;87590;87591	chr2:178557990;178557989;178557988	chr2:179422717;179422716;179422715
N2AB	27481	82666;82667;82668	chr2:178557990;178557989;178557988	chr2:179422717;179422716;179422715
N2A	26554	79885;79886;79887	chr2:178557990;178557989;178557988	chr2:179422717;179422716;179422715
N2B	20057	60394;60395;60396	chr2:178557990;178557989;178557988	chr2:179422717;179422716;179422715
Novex-1	20182	60769;60770;60771	chr2:178557990;178557989;178557988	chr2:179422717;179422716;179422715
Novex-2	20249	60970;60971;60972	chr2:178557990;178557989;178557988	chr2:179422717;179422716;179422715
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-145
• Domain position: 78
• Structural Position: 162
• Q(SASA): 0.7221
• 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
S/P	None	None	0.928	N	0.379	0.484	0.345175991111	gnomAD-4.0.0	6.84266E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99413E-07	0	0
S/T	rs1231787901	0.127	0.645	N	0.354	0.15	0.244539031024	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
S/T	rs1231787901	0.127	0.645	N	0.354	0.15	0.244539031024	gnomAD-4.0.0	6.84266E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99413E-07	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
S/A	0.0652	likely_benign	0.0611	benign	-0.228	Destabilizing	0.006	N	0.261	neutral	N	0.508145244	None	None	I
S/C	0.1052	likely_benign	0.1054	benign	-0.341	Destabilizing	0.98	D	0.413	neutral	N	0.490308501	None	None	I
S/D	0.4327	ambiguous	0.3834	ambiguous	-0.118	Destabilizing	0.83	D	0.365	neutral	None	None	None	None	I
S/E	0.5207	ambiguous	0.4701	ambiguous	-0.231	Destabilizing	0.707	D	0.366	neutral	None	None	None	None	I
S/F	0.1746	likely_benign	0.1673	benign	-1.009	Destabilizing	0.928	D	0.451	neutral	N	0.490055012	None	None	I
S/G	0.0886	likely_benign	0.086	benign	-0.24	Destabilizing	0.547	D	0.364	neutral	None	None	None	None	I
S/H	0.3218	likely_benign	0.2964	benign	-0.594	Destabilizing	0.995	D	0.395	neutral	None	None	None	None	I
S/I	0.1022	likely_benign	0.1021	benign	-0.321	Destabilizing	0.894	D	0.441	neutral	None	None	None	None	I
S/K	0.5897	likely_pathogenic	0.5487	ambiguous	-0.366	Destabilizing	0.707	D	0.367	neutral	None	None	None	None	I
S/L	0.0804	likely_benign	0.0778	benign	-0.321	Destabilizing	0.547	D	0.349	neutral	None	None	None	None	I
S/M	0.1716	likely_benign	0.1549	benign	-0.177	Destabilizing	0.985	D	0.389	neutral	None	None	None	None	I
S/N	0.1317	likely_benign	0.1246	benign	-0.112	Destabilizing	0.945	D	0.39	neutral	None	None	None	None	I
S/P	0.1897	likely_benign	0.1465	benign	-0.27	Destabilizing	0.928	D	0.379	neutral	N	0.488098046	None	None	I
S/Q	0.4427	ambiguous	0.404	ambiguous	-0.349	Destabilizing	0.945	D	0.387	neutral	None	None	None	None	I
S/R	0.5138	ambiguous	0.4897	ambiguous	-0.147	Destabilizing	0.894	D	0.381	neutral	None	None	None	None	I
S/T	0.0671	likely_benign	0.0639	benign	-0.234	Destabilizing	0.645	D	0.354	neutral	N	0.501661989	None	None	I
S/V	0.1119	likely_benign	0.1044	benign	-0.27	Destabilizing	0.809	D	0.347	neutral	None	None	None	None	I
S/W	0.3747	ambiguous	0.3688	ambiguous	-1.094	Destabilizing	0.995	D	0.654	neutral	None	None	None	None	I
S/Y	0.1869	likely_benign	0.1853	benign	-0.786	Destabilizing	0.975	D	0.463	neutral	N	0.501157827	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.