TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8977	27154;27155;27156	chr2:178713205;178713204;178713203	chr2:179577932;179577931;179577930
N2AB	8660	26203;26204;26205	chr2:178713205;178713204;178713203	chr2:179577932;179577931;179577930
N2A	7733	23422;23423;23424	chr2:178713205;178713204;178713203	chr2:179577932;179577931;179577930
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-75
• Domain position: 52
• Structural Position: 130
• Q(SASA): 0.5373
• 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/K	None	None	0.92	N	0.246	0.263	0.371344866733	gnomAD-4.0.0	1.59163E-06	None	None	None	None	N	None	0	2.28781E-05	None	0	0	None	0	0	0	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	0.1003	likely_benign	0.0929	benign	-0.284	Destabilizing	0.704	D	0.237	neutral	N	0.43853323	None	None	N
T/C	0.5918	likely_pathogenic	0.5395	ambiguous	-0.075	Destabilizing	0.999	D	0.285	neutral	None	None	None	None	N
T/D	0.4458	ambiguous	0.444	ambiguous	0.019	Stabilizing	0.884	D	0.257	neutral	None	None	None	None	N
T/E	0.3394	likely_benign	0.3341	benign	-0.073	Destabilizing	0.17	N	0.19	neutral	None	None	None	None	N
T/F	0.277	likely_benign	0.2681	benign	-0.857	Destabilizing	0.991	D	0.371	neutral	None	None	None	None	N
T/G	0.2772	likely_benign	0.2541	benign	-0.388	Destabilizing	0.939	D	0.265	neutral	None	None	None	None	N
T/H	0.2761	likely_benign	0.2607	benign	-0.737	Destabilizing	0.999	D	0.343	neutral	None	None	None	None	N
T/I	0.2489	likely_benign	0.2477	benign	-0.13	Destabilizing	0.134	N	0.165	neutral	N	0.481150644	None	None	N
T/K	0.2121	likely_benign	0.2081	benign	-0.28	Destabilizing	0.92	D	0.246	neutral	N	0.447478	None	None	N
T/L	0.1313	likely_benign	0.1235	benign	-0.13	Destabilizing	0.759	D	0.235	neutral	None	None	None	None	N
T/M	0.0994	likely_benign	0.0961	benign	0.141	Stabilizing	0.991	D	0.271	neutral	None	None	None	None	N
T/N	0.1534	likely_benign	0.1503	benign	0.022	Stabilizing	0.939	D	0.27	neutral	None	None	None	None	N
T/P	0.3616	ambiguous	0.3295	benign	-0.154	Destabilizing	0.988	D	0.291	neutral	N	0.4539454	None	None	N
T/Q	0.2348	likely_benign	0.2267	benign	-0.257	Destabilizing	0.982	D	0.289	neutral	None	None	None	None	N
T/R	0.1467	likely_benign	0.1459	benign	0.005	Stabilizing	0.976	D	0.29	neutral	N	0.44805679	None	None	N
T/S	0.1189	likely_benign	0.1069	benign	-0.154	Destabilizing	0.159	N	0.1	neutral	N	0.431471185	None	None	N
T/V	0.2022	likely_benign	0.1924	benign	-0.154	Destabilizing	0.759	D	0.211	neutral	None	None	None	None	N
T/W	0.5644	likely_pathogenic	0.5557	ambiguous	-0.884	Destabilizing	0.999	D	0.409	neutral	None	None	None	None	N
T/Y	0.3238	likely_benign	0.3204	benign	-0.589	Destabilizing	0.997	D	0.353	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.