TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14444	43555;43556;43557	chr2:178632676;178632675;178632674	chr2:179497403;179497402;179497401
N2AB	12803	38632;38633;38634	chr2:178632676;178632675;178632674	chr2:179497403;179497402;179497401
N2A	11876	35851;35852;35853	chr2:178632676;178632675;178632674	chr2:179497403;179497402;179497401
N2B	5379	16360;16361;16362	chr2:178632676;178632675;178632674	chr2:179497403;179497402;179497401
Novex-1	5504	16735;16736;16737	chr2:178632676;178632675;178632674	chr2:179497403;179497402;179497401
Novex-2	5571	16936;16937;16938	chr2:178632676;178632675;178632674	chr2:179497403;179497402;179497401
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-95
• Domain position: 37
• Structural Position: 52
• Q(SASA): 0.6988
• 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/N	rs1411904036	0.147	None	N	0.225	0.321	0.292423486923	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14784E-04	0	None	0	0	None	0	None	0	0	0
T/N	rs1411904036	0.147	None	N	0.225	0.321	0.292423486923	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	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	0.1256	likely_benign	0.1218	benign	-0.155	Destabilizing	0.027	N	0.297	neutral	N	0.480355552	None	None	N
T/C	0.6968	likely_pathogenic	0.6422	pathogenic	-0.395	Destabilizing	0.935	D	0.366	neutral	None	None	None	None	N
T/D	0.3897	ambiguous	0.3734	ambiguous	-0.025	Destabilizing	0.081	N	0.299	neutral	None	None	None	None	N
T/E	0.3419	ambiguous	0.3197	benign	-0.119	Destabilizing	0.081	N	0.294	neutral	None	None	None	None	N
T/F	0.3616	ambiguous	0.3348	benign	-0.833	Destabilizing	0.791	D	0.4	neutral	None	None	None	None	N
T/G	0.3194	likely_benign	0.2973	benign	-0.204	Destabilizing	0.035	N	0.299	neutral	None	None	None	None	N
T/H	0.3456	ambiguous	0.3146	benign	-0.354	Destabilizing	0.38	N	0.395	neutral	None	None	None	None	N
T/I	0.2879	likely_benign	0.2932	benign	-0.149	Destabilizing	0.484	N	0.386	neutral	D	0.525364136	None	None	N
T/K	0.2149	likely_benign	0.2068	benign	-0.299	Destabilizing	0.081	N	0.287	neutral	None	None	None	None	N
T/L	0.1632	likely_benign	0.1516	benign	-0.149	Destabilizing	0.149	N	0.291	neutral	None	None	None	None	N
T/M	0.1201	likely_benign	0.1105	benign	-0.182	Destabilizing	0.935	D	0.351	neutral	None	None	None	None	N
T/N	0.1173	likely_benign	0.1133	benign	-0.124	Destabilizing	None	N	0.225	neutral	N	0.443794663	None	None	N
T/P	0.1513	likely_benign	0.1378	benign	-0.128	Destabilizing	None	N	0.259	neutral	N	0.464898325	None	None	N
T/Q	0.2648	likely_benign	0.2389	benign	-0.324	Destabilizing	0.38	N	0.384	neutral	None	None	None	None	N
T/R	0.1856	likely_benign	0.1654	benign	-0.014	Destabilizing	0.38	N	0.378	neutral	None	None	None	None	N
T/S	0.1277	likely_benign	0.1209	benign	-0.278	Destabilizing	0.002	N	0.129	neutral	N	0.37382104	None	None	N
T/V	0.2684	likely_benign	0.2659	benign	-0.128	Destabilizing	0.262	N	0.244	neutral	None	None	None	None	N
T/W	0.7148	likely_pathogenic	0.6705	pathogenic	-0.93	Destabilizing	0.935	D	0.508	neutral	None	None	None	None	N
T/Y	0.3907	ambiguous	0.3729	ambiguous	-0.606	Destabilizing	0.791	D	0.397	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.