TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31763	95512;95513;95514	chr2:178545949;178545948;178545947	chr2:179410676;179410675;179410674
N2AB	30122	90589;90590;90591	chr2:178545949;178545948;178545947	chr2:179410676;179410675;179410674
N2A	29195	87808;87809;87810	chr2:178545949;178545948;178545947	chr2:179410676;179410675;179410674
N2B	22698	68317;68318;68319	chr2:178545949;178545948;178545947	chr2:179410676;179410675;179410674
Novex-1	22823	68692;68693;68694	chr2:178545949;178545948;178545947	chr2:179410676;179410675;179410674
Novex-2	22890	68893;68894;68895	chr2:178545949;178545948;178545947	chr2:179410676;179410675;179410674
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-119
• Domain position: 56
• Structural Position: 83
• Q(SASA): 0.5484
• 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
P/L	None	None	None	N	0.181	0.084	0.396494342077	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
P/S	None	None	0.012	N	0.271	0.184	0.144782658237	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
P/A	0.0618	likely_benign	0.0661	benign	-0.516	Destabilizing	0.005	N	0.215	neutral	N	0.432150683	None	None	N
P/C	0.2815	likely_benign	0.294	benign	-0.666	Destabilizing	0.864	D	0.281	neutral	None	None	None	None	N
P/D	0.2331	likely_benign	0.2357	benign	-0.404	Destabilizing	0.072	N	0.257	neutral	None	None	None	None	N
P/E	0.1327	likely_benign	0.1316	benign	-0.508	Destabilizing	0.016	N	0.249	neutral	None	None	None	None	N
P/F	0.3182	likely_benign	0.3342	benign	-0.685	Destabilizing	0.12	N	0.365	neutral	None	None	None	None	N
P/G	0.1583	likely_benign	0.1655	benign	-0.651	Destabilizing	0.031	N	0.26	neutral	None	None	None	None	N
P/H	0.1063	likely_benign	0.105	benign	-0.125	Destabilizing	0.214	N	0.289	neutral	None	None	None	None	N
P/I	0.1817	likely_benign	0.1993	benign	-0.303	Destabilizing	0.001	N	0.233	neutral	None	None	None	None	N
P/K	0.1023	likely_benign	0.1027	benign	-0.511	Destabilizing	None	N	0.093	neutral	None	None	None	None	N
P/L	0.0836	likely_benign	0.0887	benign	-0.303	Destabilizing	None	N	0.181	neutral	N	0.461646871	None	None	N
P/M	0.1772	likely_benign	0.1925	benign	-0.435	Destabilizing	0.12	N	0.307	neutral	None	None	None	None	N
P/N	0.1515	likely_benign	0.1493	benign	-0.291	Destabilizing	0.072	N	0.308	neutral	None	None	None	None	N
P/Q	0.0762	likely_benign	0.0724	benign	-0.523	Destabilizing	None	N	0.108	neutral	N	0.392208215	None	None	N
P/R	0.0874	likely_benign	0.0915	benign	0.036	Stabilizing	0.029	N	0.269	neutral	N	0.393075007	None	None	N
P/S	0.0826	likely_benign	0.0814	benign	-0.638	Destabilizing	0.012	N	0.271	neutral	N	0.400960985	None	None	N
P/T	0.0693	likely_benign	0.0715	benign	-0.641	Destabilizing	0.024	N	0.241	neutral	N	0.412407342	None	None	N
P/V	0.1225	likely_benign	0.1362	benign	-0.34	Destabilizing	0.016	N	0.217	neutral	None	None	None	None	N
P/W	0.4171	ambiguous	0.4439	ambiguous	-0.765	Destabilizing	0.864	D	0.279	neutral	None	None	None	None	N
P/Y	0.2753	likely_benign	0.2829	benign	-0.477	Destabilizing	0.356	N	0.365	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.