TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9359	28300;28301;28302	chr2:178711161;178711160;178711159	chr2:179575888;179575887;179575886
N2AB	9042	27349;27350;27351	chr2:178711161;178711160;178711159	chr2:179575888;179575887;179575886
N2A	8115	24568;24569;24570	chr2:178711161;178711160;178711159	chr2:179575888;179575887;179575886
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-79
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.1631
• 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
N/I	None	None	0.794	None	0.631	0.309	0.604580495079	gnomAD-4.0.0	6.84185E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9946E-07	0	0
N/S	rs794727988	None	0.183	None	0.518	0.131	0.159798565429	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
N/S	rs794727988	None	0.183	None	0.518	0.131	0.159798565429	gnomAD-4.0.0	1.23935E-06	None	None	None	None	N	None	1.33497E-05	0	None	0	0	None	0	0	0	1.09796E-05	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	0.2308	likely_benign	0.1826	benign	-1.259	Destabilizing	0.228	N	0.529	neutral	None	None	None	None	N
N/C	0.3324	likely_benign	0.2469	benign	-0.425	Destabilizing	0.983	D	0.658	neutral	None	None	None	None	N
N/D	0.2392	likely_benign	0.1801	benign	-1.24	Destabilizing	0.101	N	0.518	neutral	None	None	None	None	N
N/E	0.2581	likely_benign	0.2257	benign	-1.037	Destabilizing	0.004	N	0.295	neutral	None	None	None	None	N
N/F	0.4934	ambiguous	0.4476	ambiguous	-0.718	Destabilizing	0.716	D	0.623	neutral	None	None	None	None	N
N/G	0.3685	ambiguous	0.3128	benign	-1.667	Destabilizing	0.228	N	0.48	neutral	None	None	None	None	N
N/H	0.0669	likely_benign	0.0579	benign	-1.047	Destabilizing	0.004	N	0.462	neutral	None	None	None	None	N
N/I	0.2054	likely_benign	0.1609	benign	-0.174	Destabilizing	0.794	D	0.631	neutral	None	None	None	None	N
N/K	0.1898	likely_benign	0.1635	benign	-0.278	Destabilizing	0.007	N	0.313	neutral	None	None	None	None	N
N/L	0.1819	likely_benign	0.1631	benign	-0.174	Destabilizing	0.418	N	0.583	neutral	None	None	None	None	N
N/M	0.2934	likely_benign	0.2362	benign	0.125	Stabilizing	0.836	D	0.595	neutral	None	None	None	None	N
N/P	0.9235	likely_pathogenic	0.9365	pathogenic	-0.508	Destabilizing	0.593	D	0.624	neutral	None	None	None	None	N
N/Q	0.1698	likely_benign	0.1446	benign	-0.924	Destabilizing	0.004	N	0.307	neutral	None	None	None	None	N
N/R	0.1531	likely_benign	0.1537	benign	-0.357	Destabilizing	0.264	N	0.508	neutral	None	None	None	None	N
N/S	0.0975	likely_benign	0.0804	benign	-1.25	Destabilizing	0.183	N	0.518	neutral	None	None	None	None	N
N/T	0.115	likely_benign	0.0871	benign	-0.84	Destabilizing	0.351	N	0.505	neutral	None	None	None	None	N
N/V	0.2214	likely_benign	0.1657	benign	-0.508	Destabilizing	0.593	D	0.584	neutral	None	None	None	None	N
N/W	0.6528	likely_pathogenic	0.6416	pathogenic	-0.431	Destabilizing	0.983	D	0.671	neutral	None	None	None	None	N
N/Y	0.1309	likely_benign	0.1115	benign	-0.184	Destabilizing	0.487	N	0.611	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.