TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17427	52504;52505;52506	chr2:178608732;178608731;178608730	chr2:179473459;179473458;179473457
N2AB	15786	47581;47582;47583	chr2:178608732;178608731;178608730	chr2:179473459;179473458;179473457
N2A	14859	44800;44801;44802	chr2:178608732;178608731;178608730	chr2:179473459;179473458;179473457
N2B	8362	25309;25310;25311	chr2:178608732;178608731;178608730	chr2:179473459;179473458;179473457
Novex-1	8487	25684;25685;25686	chr2:178608732;178608731;178608730	chr2:179473459;179473458;179473457
Novex-2	8554	25885;25886;25887	chr2:178608732;178608731;178608730	chr2:179473459;179473458;179473457
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: Fn3-14
• Domain position: 59
• Structural Position: 88
• Q(SASA): 0.4441
• 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
H/R	rs1387146828	-0.517	0.029	N	0.253	0.179	0.245101548738	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
H/R	rs1387146828	-0.517	0.029	N	0.253	0.179	0.245101548738	gnomAD-4.0.0	1.59384E-06	None	None	None	None	I	None	0	2.28969E-05	None	0	0	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
H/A	0.1671	likely_benign	0.1934	benign	0.221	Stabilizing	0.016	N	0.303	neutral	None	None	None	None	I
H/C	0.1895	likely_benign	0.1881	benign	0.508	Stabilizing	0.864	D	0.437	neutral	None	None	None	None	I
H/D	0.162	likely_benign	0.2057	benign	-0.458	Destabilizing	0.012	N	0.36	neutral	N	0.386994397	None	None	I
H/E	0.2307	likely_benign	0.2722	benign	-0.411	Destabilizing	0.016	N	0.287	neutral	None	None	None	None	I
H/F	0.2414	likely_benign	0.2433	benign	1.105	Stabilizing	0.628	D	0.447	neutral	None	None	None	None	I
H/G	0.1622	likely_benign	0.1941	benign	-0.059	Destabilizing	None	N	0.267	neutral	None	None	None	None	I
H/I	0.2565	likely_benign	0.2639	benign	0.951	Stabilizing	0.356	N	0.472	neutral	None	None	None	None	I
H/K	0.2383	likely_benign	0.2661	benign	0.195	Stabilizing	0.016	N	0.357	neutral	None	None	None	None	I
H/L	0.1085	likely_benign	0.116	benign	0.951	Stabilizing	0.055	N	0.437	neutral	N	0.471591719	None	None	I
H/M	0.3502	ambiguous	0.3673	ambiguous	0.523	Stabilizing	0.356	N	0.42	neutral	None	None	None	None	I
H/N	0.0601	likely_benign	0.074	benign	-0.066	Destabilizing	None	N	0.105	neutral	N	0.428918377	None	None	I
H/P	0.2538	likely_benign	0.2818	benign	0.73	Stabilizing	0.106	N	0.503	neutral	N	0.45031237	None	None	I
H/Q	0.1384	likely_benign	0.1447	benign	0.069	Stabilizing	0.001	N	0.133	neutral	N	0.399422189	None	None	I
H/R	0.143	likely_benign	0.1555	benign	-0.385	Destabilizing	0.029	N	0.253	neutral	N	0.402905212	None	None	I
H/S	0.1224	likely_benign	0.1462	benign	0.116	Stabilizing	0.016	N	0.337	neutral	None	None	None	None	I
H/T	0.1603	likely_benign	0.186	benign	0.265	Stabilizing	0.038	N	0.406	neutral	None	None	None	None	I
H/V	0.1853	likely_benign	0.1959	benign	0.73	Stabilizing	0.072	N	0.487	neutral	None	None	None	None	I
H/W	0.4483	ambiguous	0.4385	ambiguous	1.135	Stabilizing	0.864	D	0.421	neutral	None	None	None	None	I
H/Y	0.1013	likely_benign	0.1017	benign	1.287	Stabilizing	0.106	N	0.36	neutral	N	0.472631869	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.