TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17384	52375;52376;52377	chr2:178608861;178608860;178608859	chr2:179473588;179473587;179473586
N2AB	15743	47452;47453;47454	chr2:178608861;178608860;178608859	chr2:179473588;179473587;179473586
N2A	14816	44671;44672;44673	chr2:178608861;178608860;178608859	chr2:179473588;179473587;179473586
N2B	8319	25180;25181;25182	chr2:178608861;178608860;178608859	chr2:179473588;179473587;179473586
Novex-1	8444	25555;25556;25557	chr2:178608861;178608860;178608859	chr2:179473588;179473587;179473586
Novex-2	8511	25756;25757;25758	chr2:178608861;178608860;178608859	chr2:179473588;179473587;179473586
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: Fn3-14
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.45
• 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
T/N	rs1307047586	-0.448	None	N	0.043	0.136	0.146414634003	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
T/N	rs1307047586	-0.448	None	N	0.043	0.136	0.146414634003	gnomAD-4.0.0	4.11044E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39928E-06	0	0
T/S	None	None	0.005	N	0.171	0.062	0.104622674875	gnomAD-4.0.0	6.85074E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99879E-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
T/A	0.1063	likely_benign	0.089	benign	-0.841	Destabilizing	0.01	N	0.204	neutral	D	0.522988905	None	None	N
T/C	0.4248	ambiguous	0.3842	ambiguous	-0.557	Destabilizing	0.628	D	0.343	neutral	None	None	None	None	N
T/D	0.2211	likely_benign	0.1984	benign	-0.214	Destabilizing	None	N	0.067	neutral	None	None	None	None	N
T/E	0.311	likely_benign	0.2955	benign	-0.239	Destabilizing	0.007	N	0.217	neutral	None	None	None	None	N
T/F	0.2745	likely_benign	0.231	benign	-1.051	Destabilizing	0.628	D	0.421	neutral	None	None	None	None	N
T/G	0.2237	likely_benign	0.1663	benign	-1.052	Destabilizing	0.007	N	0.214	neutral	None	None	None	None	N
T/H	0.2332	likely_benign	0.1895	benign	-1.359	Destabilizing	0.214	N	0.421	neutral	None	None	None	None	N
T/I	0.3026	likely_benign	0.2534	benign	-0.379	Destabilizing	0.106	N	0.367	neutral	N	0.497584704	None	None	N
T/K	0.3699	ambiguous	0.3323	benign	-0.641	Destabilizing	0.016	N	0.343	neutral	None	None	None	None	N
T/L	0.1607	likely_benign	0.1354	benign	-0.379	Destabilizing	0.031	N	0.3	neutral	None	None	None	None	N
T/M	0.1173	likely_benign	0.1023	benign	-0.001	Destabilizing	0.628	D	0.337	neutral	None	None	None	None	N
T/N	0.0569	likely_benign	0.0462	benign	-0.519	Destabilizing	None	N	0.043	neutral	N	0.456281124	None	None	N
T/P	0.5167	ambiguous	0.3748	ambiguous	-0.503	Destabilizing	0.106	N	0.337	neutral	N	0.498091683	None	None	N
T/Q	0.2672	likely_benign	0.2326	benign	-0.8	Destabilizing	0.072	N	0.307	neutral	None	None	None	None	N
T/R	0.35	ambiguous	0.3108	benign	-0.359	Destabilizing	0.031	N	0.309	neutral	None	None	None	None	N
T/S	0.0905	likely_benign	0.0771	benign	-0.827	Destabilizing	0.005	N	0.171	neutral	N	0.474789527	None	None	N
T/V	0.2263	likely_benign	0.1986	benign	-0.503	Destabilizing	0.061	N	0.149	neutral	None	None	None	None	N
T/W	0.6045	likely_pathogenic	0.5507	ambiguous	-0.929	Destabilizing	0.864	D	0.365	neutral	None	None	None	None	N
T/Y	0.2149	likely_benign	0.1836	benign	-0.698	Destabilizing	0.628	D	0.423	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.