TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23490	70693;70694;70695	chr2:178575664;178575663;178575662	chr2:179440391;179440390;179440389
N2AB	21849	65770;65771;65772	chr2:178575664;178575663;178575662	chr2:179440391;179440390;179440389
N2A	20922	62989;62990;62991	chr2:178575664;178575663;178575662	chr2:179440391;179440390;179440389
N2B	14425	43498;43499;43500	chr2:178575664;178575663;178575662	chr2:179440391;179440390;179440389
Novex-1	14550	43873;43874;43875	chr2:178575664;178575663;178575662	chr2:179440391;179440390;179440389
Novex-2	14617	44074;44075;44076	chr2:178575664;178575663;178575662	chr2:179440391;179440390;179440389
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-58
• Domain position: 56
• Structural Position: 83
• Q(SASA): 0.7188
• 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
H/D	rs1397554911	None	0.255	N	0.209	0.218	0.154104182512	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
H/D	rs1397554911	None	0.255	N	0.209	0.218	0.154104182512	gnomAD-4.0.0	3.84475E-06	None	None	None	None	N	None	1.69291E-05	0	None	0	0	None	0	0	2.39383E-06	0	2.84511E-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
H/A	0.1627	likely_benign	0.1687	benign	0.487	Stabilizing	0.248	N	0.199	neutral	None	None	None	None	N
H/C	0.167	likely_benign	0.1583	benign	0.889	Stabilizing	0.989	D	0.217	neutral	None	None	None	None	N
H/D	0.2254	likely_benign	0.2104	benign	0.143	Stabilizing	0.255	N	0.209	neutral	N	0.461836085	None	None	N
H/E	0.2725	likely_benign	0.2649	benign	0.153	Stabilizing	0.12	N	0.097	neutral	None	None	None	None	N
H/F	0.2527	likely_benign	0.2658	benign	1.0	Stabilizing	0.978	D	0.333	neutral	None	None	None	None	N
H/G	0.1799	likely_benign	0.1762	benign	0.227	Stabilizing	0.43	N	0.206	neutral	None	None	None	None	N
H/I	0.2278	likely_benign	0.2395	benign	1.135	Stabilizing	0.747	D	0.306	neutral	None	None	None	None	N
H/K	0.2761	likely_benign	0.2461	benign	0.469	Stabilizing	0.231	N	0.206	neutral	None	None	None	None	N
H/L	0.0868	likely_benign	0.0908	benign	1.135	Stabilizing	0.312	N	0.239	neutral	N	0.483675582	None	None	N
H/M	0.2992	likely_benign	0.3237	benign	0.901	Stabilizing	0.912	D	0.246	neutral	None	None	None	None	N
H/N	0.0708	likely_benign	0.0719	benign	0.522	Stabilizing	0.255	N	0.153	neutral	N	0.397747321	None	None	N
H/P	0.0702	likely_benign	0.0692	benign	0.945	Stabilizing	0.627	D	0.285	neutral	N	0.422048333	None	None	N
H/Q	0.124	likely_benign	0.1243	benign	0.586	Stabilizing	0.002	N	0.106	neutral	N	0.453832677	None	None	N
H/R	0.1513	likely_benign	0.1274	benign	-0.089	Destabilizing	0.185	N	0.14	neutral	N	0.421202971	None	None	N
H/S	0.1089	likely_benign	0.111	benign	0.611	Stabilizing	0.02	N	0.123	neutral	None	None	None	None	N
H/T	0.1414	likely_benign	0.1438	benign	0.717	Stabilizing	0.185	N	0.211	neutral	None	None	None	None	N
H/V	0.1806	likely_benign	0.1911	benign	0.945	Stabilizing	0.603	D	0.272	neutral	None	None	None	None	N
H/W	0.3897	ambiguous	0.387	ambiguous	0.928	Stabilizing	0.998	D	0.221	neutral	None	None	None	None	N
H/Y	0.1099	likely_benign	0.11	benign	1.257	Stabilizing	0.905	D	0.192	neutral	N	0.492564424	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.