TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24080	72463;72464;72465	chr2:178573894;178573893;178573892	chr2:179438621;179438620;179438619
N2AB	22439	67540;67541;67542	chr2:178573894;178573893;178573892	chr2:179438621;179438620;179438619
N2A	21512	64759;64760;64761	chr2:178573894;178573893;178573892	chr2:179438621;179438620;179438619
N2B	15015	45268;45269;45270	chr2:178573894;178573893;178573892	chr2:179438621;179438620;179438619
Novex-1	15140	45643;45644;45645	chr2:178573894;178573893;178573892	chr2:179438621;179438620;179438619
Novex-2	15207	45844;45845;45846	chr2:178573894;178573893;178573892	chr2:179438621;179438620;179438619
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-131
• Domain position: 52
• Structural Position: 127
• Q(SASA): 0.3634
• 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
I/T	None	None	None	N	0.331	0.099	0.298403945805	gnomAD-4.0.0	1.59775E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8735E-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
I/A	0.1556	likely_benign	0.1808	benign	-0.651	Destabilizing	0.016	N	0.479	neutral	None	None	None	None	N
I/C	0.5869	likely_pathogenic	0.6344	pathogenic	-0.595	Destabilizing	0.356	N	0.507	neutral	None	None	None	None	N
I/D	0.4532	ambiguous	0.4854	ambiguous	-0.108	Destabilizing	0.038	N	0.57	neutral	None	None	None	None	N
I/E	0.312	likely_benign	0.319	benign	-0.204	Destabilizing	0.072	N	0.57	neutral	None	None	None	None	N
I/F	0.1137	likely_benign	0.1394	benign	-0.709	Destabilizing	0.171	N	0.462	neutral	N	0.44953687	None	None	N
I/G	0.4418	ambiguous	0.4934	ambiguous	-0.818	Destabilizing	0.038	N	0.575	neutral	None	None	None	None	N
I/H	0.3174	likely_benign	0.3459	ambiguous	-0.16	Destabilizing	0.356	N	0.573	neutral	None	None	None	None	N
I/K	0.1803	likely_benign	0.1897	benign	-0.288	Destabilizing	0.072	N	0.578	neutral	None	None	None	None	N
I/L	0.0977	likely_benign	0.1169	benign	-0.338	Destabilizing	0.002	N	0.241	neutral	N	0.455732124	None	None	N
I/M	0.0693	likely_benign	0.0751	benign	-0.319	Destabilizing	0.002	N	0.244	neutral	N	0.483188084	None	None	N
I/N	0.145	likely_benign	0.1561	benign	-0.058	Destabilizing	None	N	0.435	neutral	N	0.381330366	None	None	N
I/P	0.466	ambiguous	0.5584	ambiguous	-0.409	Destabilizing	0.356	N	0.593	neutral	None	None	None	None	N
I/Q	0.2528	likely_benign	0.2613	benign	-0.299	Destabilizing	0.356	N	0.588	neutral	None	None	None	None	N
I/R	0.1492	likely_benign	0.1657	benign	0.252	Stabilizing	0.072	N	0.588	neutral	None	None	None	None	N
I/S	0.1498	likely_benign	0.1746	benign	-0.536	Destabilizing	0.012	N	0.587	neutral	N	0.384101312	None	None	N
I/T	0.073	likely_benign	0.0953	benign	-0.521	Destabilizing	None	N	0.331	neutral	N	0.39603046	None	None	N
I/V	0.0799	likely_benign	0.0882	benign	-0.409	Destabilizing	0.005	N	0.258	neutral	N	0.458481641	None	None	N
I/W	0.5645	likely_pathogenic	0.6034	pathogenic	-0.718	Destabilizing	0.864	D	0.583	neutral	None	None	None	None	N
I/Y	0.3217	likely_benign	0.3427	ambiguous	-0.45	Destabilizing	0.356	N	0.521	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.