TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17035	51328;51329;51330	chr2:178611026;178611025;178611024	chr2:179475753;179475752;179475751
N2AB	15394	46405;46406;46407	chr2:178611026;178611025;178611024	chr2:179475753;179475752;179475751
N2A	14467	43624;43625;43626	chr2:178611026;178611025;178611024	chr2:179475753;179475752;179475751
N2B	7970	24133;24134;24135	chr2:178611026;178611025;178611024	chr2:179475753;179475752;179475751
Novex-1	8095	24508;24509;24510	chr2:178611026;178611025;178611024	chr2:179475753;179475752;179475751
Novex-2	8162	24709;24710;24711	chr2:178611026;178611025;178611024	chr2:179475753;179475752;179475751
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-111
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.47
• Predicted PPI site: I

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/P	None	None	0.988	D	0.438	0.503	0.344483371355	gnomAD-4.0.0	1.59388E-06	None	None	None	None	I	None	0	0	None	0	2.77917E-05	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
S/A	0.0702	likely_benign	0.0747	benign	-0.427	Destabilizing	0.061	N	0.143	neutral	N	0.512313459	None	None	I
S/C	0.1092	likely_benign	0.107	benign	-0.316	Destabilizing	0.999	D	0.467	neutral	None	None	None	None	I
S/D	0.4364	ambiguous	0.4528	ambiguous	-0.175	Destabilizing	0.969	D	0.358	neutral	None	None	None	None	I
S/E	0.4218	ambiguous	0.4221	ambiguous	-0.272	Destabilizing	0.969	D	0.365	neutral	None	None	None	None	I
S/F	0.1616	likely_benign	0.1621	benign	-0.973	Destabilizing	0.982	D	0.566	neutral	None	None	None	None	I
S/G	0.1093	likely_benign	0.1112	benign	-0.542	Destabilizing	0.884	D	0.298	neutral	None	None	None	None	I
S/H	0.2947	likely_benign	0.2827	benign	-1.056	Destabilizing	0.999	D	0.468	neutral	None	None	None	None	I
S/I	0.1262	likely_benign	0.139	benign	-0.249	Destabilizing	0.964	D	0.509	neutral	None	None	None	None	I
S/K	0.448	ambiguous	0.4544	ambiguous	-0.602	Destabilizing	0.939	D	0.363	neutral	None	None	None	None	I
S/L	0.0811	likely_benign	0.0859	benign	-0.249	Destabilizing	0.704	D	0.487	neutral	D	0.630674818	None	None	I
S/M	0.1497	likely_benign	0.1626	benign	0.087	Stabilizing	0.759	D	0.403	neutral	None	None	None	None	I
S/N	0.1303	likely_benign	0.1423	benign	-0.307	Destabilizing	0.969	D	0.408	neutral	None	None	None	None	I
S/P	0.5966	likely_pathogenic	0.571	pathogenic	-0.28	Destabilizing	0.988	D	0.438	neutral	D	0.544227077	None	None	I
S/Q	0.3856	ambiguous	0.3844	ambiguous	-0.628	Destabilizing	0.991	D	0.405	neutral	None	None	None	None	I
S/R	0.4407	ambiguous	0.4217	ambiguous	-0.318	Destabilizing	0.991	D	0.452	neutral	None	None	None	None	I
S/T	0.0677	likely_benign	0.0709	benign	-0.411	Destabilizing	0.134	N	0.176	neutral	N	0.513654969	None	None	I
S/V	0.1314	likely_benign	0.1452	benign	-0.28	Destabilizing	0.884	D	0.509	neutral	None	None	None	None	I
S/W	0.391	ambiguous	0.3443	ambiguous	-0.95	Destabilizing	0.999	D	0.62	neutral	None	None	None	None	I
S/Y	0.1911	likely_benign	0.1796	benign	-0.692	Destabilizing	0.997	D	0.569	neutral	None	None	None	None	I

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.