TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29171	87736;87737;87738	chr2:178557843;178557842;178557841	chr2:179422570;179422569;179422568
N2AB	27530	82813;82814;82815	chr2:178557843;178557842;178557841	chr2:179422570;179422569;179422568
N2A	26603	80032;80033;80034	chr2:178557843;178557842;178557841	chr2:179422570;179422569;179422568
N2B	20106	60541;60542;60543	chr2:178557843;178557842;178557841	chr2:179422570;179422569;179422568
Novex-1	20231	60916;60917;60918	chr2:178557843;178557842;178557841	chr2:179422570;179422569;179422568
Novex-2	20298	61117;61118;61119	chr2:178557843;178557842;178557841	chr2:179422570;179422569;179422568
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-100
• Domain position: 35
• Structural Position: 36
• Q(SASA): 0.3728
• 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
T/A	rs1474922930	-0.827	0.999	N	0.579	0.542	0.388970301349	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	9.94E-05	0	None	0	None	0	0	0
T/A	rs1474922930	-0.827	0.999	N	0.579	0.542	0.388970301349	gnomAD-4.0.0	1.36834E-06	None	None	None	None	I	None	0	0	None	3.82643E-05	0	None	0	0	8.99431E-07	0	0
T/S	None	None	0.999	N	0.569	0.443	0.341226946553	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
T/A	0.265	likely_benign	0.3987	ambiguous	-0.51	Destabilizing	0.999	D	0.579	neutral	N	0.485691286	None	None	I
T/C	0.753	likely_pathogenic	0.8483	pathogenic	-0.246	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	I
T/D	0.8634	likely_pathogenic	0.9189	pathogenic	-0.286	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	I
T/E	0.8433	likely_pathogenic	0.9113	pathogenic	-0.353	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
T/F	0.7647	likely_pathogenic	0.8676	pathogenic	-0.875	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	I
T/G	0.5168	ambiguous	0.626	pathogenic	-0.678	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
T/H	0.6914	likely_pathogenic	0.7836	pathogenic	-1.042	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
T/I	0.6754	likely_pathogenic	0.8084	pathogenic	-0.174	Destabilizing	1.0	D	0.855	deleterious	N	0.515097354	None	None	I
T/K	0.7235	likely_pathogenic	0.7945	pathogenic	-0.582	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	I
T/L	0.3232	likely_benign	0.4723	ambiguous	-0.174	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	I
T/M	0.207	likely_benign	0.3052	benign	0.217	Stabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
T/N	0.2624	likely_benign	0.365	ambiguous	-0.349	Destabilizing	1.0	D	0.807	deleterious	N	0.498127746	None	None	I
T/P	0.7897	likely_pathogenic	0.8395	pathogenic	-0.256	Destabilizing	1.0	D	0.844	deleterious	N	0.510342907	None	None	I
T/Q	0.5962	likely_pathogenic	0.7004	pathogenic	-0.654	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	I
T/R	0.6724	likely_pathogenic	0.7543	pathogenic	-0.236	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
T/S	0.1904	likely_benign	0.266	benign	-0.543	Destabilizing	0.999	D	0.569	neutral	N	0.448333644	None	None	I
T/V	0.5165	ambiguous	0.6742	pathogenic	-0.256	Destabilizing	0.999	D	0.654	neutral	None	None	None	None	I
T/W	0.9341	likely_pathogenic	0.9615	pathogenic	-0.832	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
T/Y	0.7759	likely_pathogenic	0.8703	pathogenic	-0.585	Destabilizing	1.0	D	0.857	deleterious	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.