TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7658	23197;23198;23199	chr2:178721047;178721046;178721045	chr2:179585774;179585773;179585772
N2AB	7341	22246;22247;22248	chr2:178721047;178721046;178721045	chr2:179585774;179585773;179585772
N2A	6414	19465;19466;19467	chr2:178721047;178721046;178721045	chr2:179585774;179585773;179585772
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: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-61
• Domain position: 51
• Structural Position: 125
• Q(SASA): 0.3587
• 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/L	None	None	0.016	N	0.319	0.306	0.55355060856	gnomAD-4.0.0	1.36886E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79954E-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	0.0879	likely_benign	0.0859	benign	-0.387	Destabilizing	0.001	N	0.13	neutral	N	0.50975861	None	None	N
S/C	0.2036	likely_benign	0.1817	benign	-0.285	Destabilizing	0.994	D	0.393	neutral	None	None	None	None	N
S/D	0.3172	likely_benign	0.3924	ambiguous	0.28	Stabilizing	0.486	N	0.347	neutral	None	None	None	None	N
S/E	0.4062	ambiguous	0.4967	ambiguous	0.251	Stabilizing	0.726	D	0.319	neutral	None	None	None	None	N
S/F	0.1867	likely_benign	0.2066	benign	-0.692	Destabilizing	0.961	D	0.499	neutral	None	None	None	None	N
S/G	0.1374	likely_benign	0.146	benign	-0.596	Destabilizing	0.591	D	0.351	neutral	None	None	None	None	N
S/H	0.2464	likely_benign	0.291	benign	-1.025	Destabilizing	0.995	D	0.399	neutral	None	None	None	None	N
S/I	0.1832	likely_benign	0.2068	benign	0.046	Stabilizing	0.78	D	0.456	neutral	None	None	None	None	N
S/K	0.4608	ambiguous	0.5862	pathogenic	-0.464	Destabilizing	0.876	D	0.319	neutral	None	None	None	None	N
S/L	0.1244	likely_benign	0.1283	benign	0.046	Stabilizing	0.016	N	0.319	neutral	N	0.510452043	None	None	N
S/M	0.2085	likely_benign	0.2177	benign	0.09	Stabilizing	0.961	D	0.407	neutral	None	None	None	None	N
S/N	0.1357	likely_benign	0.1563	benign	-0.323	Destabilizing	0.003	N	0.225	neutral	None	None	None	None	N
S/P	0.8763	likely_pathogenic	0.9295	pathogenic	-0.064	Destabilizing	0.91	D	0.383	neutral	N	0.504445829	None	None	N
S/Q	0.3824	ambiguous	0.4334	ambiguous	-0.433	Destabilizing	0.98	D	0.387	neutral	None	None	None	None	N
S/R	0.3848	ambiguous	0.4892	ambiguous	-0.364	Destabilizing	0.961	D	0.383	neutral	None	None	None	None	N
S/T	0.0755	likely_benign	0.0827	benign	-0.363	Destabilizing	0.001	N	0.099	neutral	N	0.452787819	None	None	N
S/V	0.1821	likely_benign	0.1889	benign	-0.064	Destabilizing	0.57	D	0.445	neutral	None	None	None	None	N
S/W	0.3242	likely_benign	0.3743	ambiguous	-0.73	Destabilizing	0.998	D	0.597	neutral	None	None	None	None	N
S/Y	0.158	likely_benign	0.1799	benign	-0.433	Destabilizing	0.994	D	0.504	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.