TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22622	68089;68090;68091	chr2:178579166;178579165;178579164	chr2:179443893;179443892;179443891
N2AB	20981	63166;63167;63168	chr2:178579166;178579165;178579164	chr2:179443893;179443892;179443891
N2A	20054	60385;60386;60387	chr2:178579166;178579165;178579164	chr2:179443893;179443892;179443891
N2B	13557	40894;40895;40896	chr2:178579166;178579165;178579164	chr2:179443893;179443892;179443891
Novex-1	13682	41269;41270;41271	chr2:178579166;178579165;178579164	chr2:179443893;179443892;179443891
Novex-2	13749	41470;41471;41472	chr2:178579166;178579165;178579164	chr2:179443893;179443892;179443891
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-127
• Domain position: 63
• Structural Position: 155
• Q(SASA): 0.2161
• 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/A	None	None	0.989	N	0.507	0.362	0.303123707472	gnomAD-4.0.0	3.18415E-06	None	None	None	None	N	None	5.66316E-05	0	None	0	0	None	0	0	2.85995E-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	0.0891	likely_benign	0.0869	benign	-1.326	Destabilizing	0.989	D	0.507	neutral	N	0.473168167	None	None	N
T/C	0.3197	likely_benign	0.3022	benign	-1.057	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	N
T/D	0.5426	ambiguous	0.5153	ambiguous	-1.456	Destabilizing	0.995	D	0.603	neutral	None	None	None	None	N
T/E	0.4145	ambiguous	0.3855	ambiguous	-1.285	Destabilizing	0.998	D	0.602	neutral	None	None	None	None	N
T/F	0.2575	likely_benign	0.2473	benign	-1.075	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
T/G	0.256	likely_benign	0.2388	benign	-1.704	Destabilizing	0.992	D	0.577	neutral	None	None	None	None	N
T/H	0.2355	likely_benign	0.2168	benign	-1.783	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
T/I	0.1353	likely_benign	0.1361	benign	-0.343	Destabilizing	0.978	D	0.572	neutral	N	0.462292387	None	None	N
T/K	0.2003	likely_benign	0.1879	benign	-0.608	Destabilizing	0.997	D	0.605	neutral	N	0.461051393	None	None	N
T/L	0.1135	likely_benign	0.113	benign	-0.343	Destabilizing	0.983	D	0.51	neutral	None	None	None	None	N
T/M	0.0988	likely_benign	0.1032	benign	-0.339	Destabilizing	1.0	D	0.648	neutral	None	None	None	None	N
T/N	0.1615	likely_benign	0.1554	benign	-1.169	Destabilizing	0.784	D	0.379	neutral	None	None	None	None	N
T/P	0.4672	ambiguous	0.5247	ambiguous	-0.641	Destabilizing	0.999	D	0.649	neutral	N	0.497148225	None	None	N
T/Q	0.2365	likely_benign	0.2208	benign	-1.067	Destabilizing	0.999	D	0.655	neutral	None	None	None	None	N
T/R	0.1543	likely_benign	0.1469	benign	-0.704	Destabilizing	0.998	D	0.651	neutral	N	0.510621749	None	None	N
T/S	0.1243	likely_benign	0.1188	benign	-1.428	Destabilizing	0.989	D	0.507	neutral	N	0.459138835	None	None	N
T/V	0.1095	likely_benign	0.1154	benign	-0.641	Destabilizing	0.611	D	0.417	neutral	None	None	None	None	N
T/W	0.6018	likely_pathogenic	0.5895	pathogenic	-1.131	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
T/Y	0.3076	likely_benign	0.2994	benign	-0.784	Destabilizing	1.0	D	0.705	prob.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.