TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5136	15631;15632;15633	chr2:178734418;178734417;178734416	chr2:179599145;179599144;179599143
N2AB	4819	14680;14681;14682	chr2:178734418;178734417;178734416	chr2:179599145;179599144;179599143
N2A	3892	11899;11900;11901	chr2:178734418;178734417;178734416	chr2:179599145;179599144;179599143
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: TCG
• RefSeq wild type template codon: AGC
• Domain: Ig-34
• Domain position: 62
• Structural Position: 143
• Q(SASA): 0.5668
• 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	rs764310312	-0.265	0.993	D	0.522	0.493	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
S/L	rs764310312	-0.265	0.993	D	0.522	0.493	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
S/L	rs764310312	-0.265	0.993	D	0.522	0.493	None	gnomAD-4.0.0	9.29666E-06	None	None	None	None	N	None	6.67717E-05	1.66728E-05	None	0	0	None	0	0	6.78143E-06	0	1.60118E-05

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	0.0645	likely_benign	0.0757	benign	-0.608	Destabilizing	0.91	D	0.449	neutral	N	0.51101014	None	None	N
S/C	0.1142	likely_benign	0.127	benign	-0.345	Destabilizing	1.0	D	0.518	neutral	None	None	None	None	N
S/D	0.6298	likely_pathogenic	0.658	pathogenic	-0.233	Destabilizing	0.985	D	0.426	neutral	None	None	None	None	N
S/E	0.7491	likely_pathogenic	0.7839	pathogenic	-0.304	Destabilizing	0.985	D	0.411	neutral	None	None	None	None	N
S/F	0.1972	likely_benign	0.2586	benign	-1.159	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	N
S/G	0.0892	likely_benign	0.1034	benign	-0.755	Destabilizing	0.985	D	0.451	neutral	None	None	None	None	N
S/H	0.4519	ambiguous	0.4906	ambiguous	-1.338	Destabilizing	1.0	D	0.514	neutral	None	None	None	None	N
S/I	0.2226	likely_benign	0.289	benign	-0.341	Destabilizing	0.991	D	0.572	neutral	None	None	None	None	N
S/K	0.8673	likely_pathogenic	0.8939	pathogenic	-0.589	Destabilizing	0.97	D	0.411	neutral	None	None	None	None	N
S/L	0.0925	likely_benign	0.1103	benign	-0.341	Destabilizing	0.993	D	0.522	neutral	D	0.523115023	None	None	N
S/M	0.1931	likely_benign	0.2458	benign	0.155	Stabilizing	1.0	D	0.514	neutral	None	None	None	None	N
S/N	0.1816	likely_benign	0.2009	benign	-0.409	Destabilizing	0.985	D	0.451	neutral	None	None	None	None	N
S/P	0.4057	ambiguous	0.524	ambiguous	-0.401	Destabilizing	0.998	D	0.46	neutral	N	0.51781075	None	None	N
S/Q	0.5888	likely_pathogenic	0.6421	pathogenic	-0.709	Destabilizing	0.999	D	0.448	neutral	None	None	None	None	N
S/R	0.8128	likely_pathogenic	0.8221	pathogenic	-0.358	Destabilizing	0.996	D	0.474	neutral	None	None	None	None	N
S/T	0.0906	likely_benign	0.107	benign	-0.49	Destabilizing	0.122	N	0.188	neutral	N	0.50361136	None	None	N
S/V	0.1784	likely_benign	0.2342	benign	-0.401	Destabilizing	0.97	D	0.529	neutral	None	None	None	None	N
S/W	0.3989	ambiguous	0.4651	ambiguous	-1.118	Destabilizing	1.0	D	0.756	deleterious	D	0.587782055	None	None	N
S/Y	0.1991	likely_benign	0.232	benign	-0.852	Destabilizing	0.999	D	0.653	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.