TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4728	14407;14408;14409	chr2:178738271;178738270;178738269	chr2:179602998;179602997;179602996
N2AB	4411	13456;13457;13458	chr2:178738271;178738270;178738269	chr2:179602998;179602997;179602996
N2A	3484	10675;10676;10677	chr2:178738271;178738270;178738269	chr2:179602998;179602997;179602996
N2B	4365	13318;13319;13320	chr2:178738271;178738270;178738269	chr2:179602998;179602997;179602996
Novex-1	4490	13693;13694;13695	chr2:178738271;178738270;178738269	chr2:179602998;179602997;179602996
Novex-2	4557	13894;13895;13896	chr2:178738271;178738270;178738269	chr2:179602998;179602997;179602996
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-30
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.905
• 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
N/T	None	None	0.024	N	0.285	0.072	0.233150807113	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
N/A	0.1651	likely_benign	0.1854	benign	-0.205	Destabilizing	0.016	N	0.473	neutral	None	None	None	None	I
N/C	0.3421	ambiguous	0.3769	ambiguous	0.302	Stabilizing	0.864	D	0.471	neutral	None	None	None	None	I
N/D	0.0961	likely_benign	0.1175	benign	0.067	Stabilizing	None	N	0.148	neutral	N	0.487698205	None	None	I
N/E	0.3076	likely_benign	0.3432	ambiguous	0.029	Stabilizing	0.016	N	0.307	neutral	None	None	None	None	I
N/F	0.494	ambiguous	0.5632	ambiguous	-0.626	Destabilizing	0.214	N	0.485	neutral	None	None	None	None	I
N/G	0.202	likely_benign	0.2306	benign	-0.363	Destabilizing	None	N	0.127	neutral	None	None	None	None	I
N/H	0.1061	likely_benign	0.1127	benign	-0.414	Destabilizing	0.295	N	0.369	neutral	N	0.49177538	None	None	I
N/I	0.2657	likely_benign	0.3107	benign	0.121	Stabilizing	0.029	N	0.509	neutral	N	0.492248918	None	None	I
N/K	0.2284	likely_benign	0.2386	benign	0.024	Stabilizing	None	N	0.211	neutral	N	0.487698205	None	None	I
N/L	0.2468	likely_benign	0.2763	benign	0.121	Stabilizing	None	N	0.305	neutral	None	None	None	None	I
N/M	0.3463	ambiguous	0.3789	ambiguous	0.263	Stabilizing	0.214	N	0.479	neutral	None	None	None	None	I
N/P	0.5599	ambiguous	0.6365	pathogenic	0.038	Stabilizing	0.356	N	0.494	neutral	None	None	None	None	I
N/Q	0.2998	likely_benign	0.3143	benign	-0.309	Destabilizing	0.038	N	0.341	neutral	None	None	None	None	I
N/R	0.2633	likely_benign	0.28	benign	0.056	Stabilizing	0.038	N	0.333	neutral	None	None	None	None	I
N/S	0.0771	likely_benign	0.0835	benign	-0.087	Destabilizing	0.002	N	0.129	neutral	N	0.48969392	None	None	I
N/T	0.1321	likely_benign	0.1486	benign	0.004	Stabilizing	0.024	N	0.285	neutral	N	0.488746398	None	None	I
N/V	0.239	likely_benign	0.2664	benign	0.038	Stabilizing	0.038	N	0.507	neutral	None	None	None	None	I
N/W	0.7563	likely_pathogenic	0.8013	pathogenic	-0.69	Destabilizing	0.864	D	0.499	neutral	None	None	None	None	I
N/Y	0.1651	likely_benign	0.1921	benign	-0.402	Destabilizing	0.56	D	0.485	neutral	N	0.492248918	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.