TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8723	26392;26393;26394	chr2:178715019;178715018;178715017	chr2:179579746;179579745;179579744
N2AB	8406	25441;25442;25443	chr2:178715019;178715018;178715017	chr2:179579746;179579745;179579744
N2A	7479	22660;22661;22662	chr2:178715019;178715018;178715017	chr2:179579746;179579745;179579744
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: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-72
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.4158
• 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/R	rs1304915212	None	0.011	D	0.281	0.172	0.0846915920261	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
S/R	rs1304915212	None	0.011	D	0.281	0.172	0.0846915920261	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.0771	likely_benign	0.0961	benign	-0.496	Destabilizing	0.003	N	0.398	neutral	None	None	None	None	I
S/C	0.1535	likely_benign	0.1857	benign	-0.295	Destabilizing	0.818	D	0.557	neutral	D	0.544377322	None	None	I
S/D	0.4379	ambiguous	0.5925	pathogenic	-0.343	Destabilizing	0.181	N	0.443	neutral	None	None	None	None	I
S/E	0.4649	ambiguous	0.5948	pathogenic	-0.436	Destabilizing	0.237	N	0.425	neutral	None	None	None	None	I
S/F	0.1375	likely_benign	0.1677	benign	-1.046	Destabilizing	0.855	D	0.634	neutral	None	None	None	None	I
S/G	0.1079	likely_benign	0.1283	benign	-0.619	Destabilizing	0.001	N	0.145	neutral	D	0.525259109	None	None	I
S/H	0.3327	likely_benign	0.4088	ambiguous	-1.157	Destabilizing	0.985	D	0.544	neutral	None	None	None	None	I
S/I	0.1387	likely_benign	0.173	benign	-0.295	Destabilizing	0.523	D	0.63	neutral	N	0.50462364	None	None	I
S/K	0.5779	likely_pathogenic	0.7248	pathogenic	-0.649	Destabilizing	0.293	N	0.388	neutral	None	None	None	None	I
S/L	0.0902	likely_benign	0.1062	benign	-0.295	Destabilizing	0.293	N	0.58	neutral	None	None	None	None	I
S/M	0.1552	likely_benign	0.1742	benign	0.146	Stabilizing	0.957	D	0.544	neutral	None	None	None	None	I
S/N	0.1286	likely_benign	0.1527	benign	-0.369	Destabilizing	0.019	N	0.468	neutral	N	0.492253376	None	None	I
S/P	0.6871	likely_pathogenic	0.8358	pathogenic	-0.334	Destabilizing	0.612	D	0.533	neutral	None	None	None	None	I
S/Q	0.4328	ambiguous	0.5212	ambiguous	-0.711	Destabilizing	0.744	D	0.481	neutral	None	None	None	None	I
S/R	0.496	ambiguous	0.6566	pathogenic	-0.343	Destabilizing	0.011	N	0.281	neutral	D	0.525978856	None	None	I
S/T	0.0725	likely_benign	0.0748	benign	-0.456	Destabilizing	None	N	0.19	neutral	N	0.485940388	None	None	I
S/V	0.1425	likely_benign	0.1758	benign	-0.334	Destabilizing	0.134	N	0.564	neutral	None	None	None	None	I
S/W	0.2852	likely_benign	0.3698	ambiguous	-1.014	Destabilizing	0.985	D	0.697	prob.neutral	None	None	None	None	I
S/Y	0.1584	likely_benign	0.2039	benign	-0.76	Destabilizing	0.855	D	0.635	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.