TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18024	54295;54296;54297	chr2:178605107;178605106;178605105	chr2:179469834;179469833;179469832
N2AB	16383	49372;49373;49374	chr2:178605107;178605106;178605105	chr2:179469834;179469833;179469832
N2A	15456	46591;46592;46593	chr2:178605107;178605106;178605105	chr2:179469834;179469833;179469832
N2B	8959	27100;27101;27102	chr2:178605107;178605106;178605105	chr2:179469834;179469833;179469832
Novex-1	9084	27475;27476;27477	chr2:178605107;178605106;178605105	chr2:179469834;179469833;179469832
Novex-2	9151	27676;27677;27678	chr2:178605107;178605106;178605105	chr2:179469834;179469833;179469832
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-114
• Domain position: 57
• Structural Position: 130
• Q(SASA): 0.0763
• 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
S/G	None	None	0.024	N	0.453	0.085	0.124217242631	gnomAD-4.0.0	1.59334E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86229E-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
S/A	0.1087	likely_benign	0.1083	benign	-0.582	Destabilizing	0.007	N	0.365	neutral	None	None	None	None	N
S/C	0.2614	likely_benign	0.2358	benign	-0.403	Destabilizing	0.295	N	0.589	neutral	N	0.497249807	None	None	N
S/D	0.6998	likely_pathogenic	0.6705	pathogenic	-0.437	Destabilizing	0.072	N	0.479	neutral	None	None	None	None	N
S/E	0.7104	likely_pathogenic	0.7027	pathogenic	-0.495	Destabilizing	0.072	N	0.46	neutral	None	None	None	None	N
S/F	0.4366	ambiguous	0.4109	ambiguous	-0.981	Destabilizing	0.072	N	0.609	neutral	None	None	None	None	N
S/G	0.15	likely_benign	0.1508	benign	-0.76	Destabilizing	0.024	N	0.453	neutral	N	0.465540033	None	None	N
S/H	0.5782	likely_pathogenic	0.5607	ambiguous	-1.346	Destabilizing	0.628	D	0.588	neutral	None	None	None	None	N
S/I	0.3453	ambiguous	0.2989	benign	-0.229	Destabilizing	0.012	N	0.517	neutral	N	0.459635568	None	None	N
S/K	0.8345	likely_pathogenic	0.8284	pathogenic	-0.721	Destabilizing	0.031	N	0.449	neutral	None	None	None	None	N
S/L	0.1871	likely_benign	0.1717	benign	-0.229	Destabilizing	None	N	0.431	neutral	None	None	None	None	N
S/M	0.2555	likely_benign	0.2484	benign	0.202	Stabilizing	0.001	N	0.404	neutral	None	None	None	None	N
S/N	0.2496	likely_benign	0.2274	benign	-0.539	Destabilizing	0.055	N	0.473	neutral	N	0.433043613	None	None	N
S/P	0.8169	likely_pathogenic	0.7739	pathogenic	-0.316	Destabilizing	0.136	N	0.588	neutral	None	None	None	None	N
S/Q	0.6078	likely_pathogenic	0.6252	pathogenic	-0.841	Destabilizing	0.136	N	0.543	neutral	None	None	None	None	N
S/R	0.7904	likely_pathogenic	0.7893	pathogenic	-0.498	Destabilizing	0.055	N	0.588	neutral	N	0.440009657	None	None	N
S/T	0.0968	likely_benign	0.0912	benign	-0.586	Destabilizing	None	N	0.175	neutral	N	0.389639552	None	None	N
S/V	0.2985	likely_benign	0.2668	benign	-0.316	Destabilizing	None	N	0.449	neutral	None	None	None	None	N
S/W	0.5294	ambiguous	0.4955	ambiguous	-0.943	Destabilizing	0.864	D	0.609	neutral	None	None	None	None	N
S/Y	0.3592	ambiguous	0.3338	benign	-0.687	Destabilizing	0.356	N	0.636	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.