TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22071	66436;66437;66438	chr2:178582158;178582157;178582156	chr2:179446885;179446884;179446883
N2AB	20430	61513;61514;61515	chr2:178582158;178582157;178582156	chr2:179446885;179446884;179446883
N2A	19503	58732;58733;58734	chr2:178582158;178582157;178582156	chr2:179446885;179446884;179446883
N2B	13006	39241;39242;39243	chr2:178582158;178582157;178582156	chr2:179446885;179446884;179446883
Novex-1	13131	39616;39617;39618	chr2:178582158;178582157;178582156	chr2:179446885;179446884;179446883
Novex-2	13198	39817;39818;39819	chr2:178582158;178582157;178582156	chr2:179446885;179446884;179446883
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Fn3-48
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.3554
• 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/P	rs968902463	None	0.523	N	0.639	0.234	0.367425347029	gnomAD-4.0.0	6.84663E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99705E-07	0	0
H/R	rs968902463	None	0.351	N	0.354	0.138	0.244539031024	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
H/R	rs968902463	None	0.351	N	0.354	0.138	0.244539031024	gnomAD-4.0.0	1.86024E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.54347E-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
H/A	0.3016	likely_benign	0.3364	benign	-0.804	Destabilizing	0.061	N	0.321	neutral	None	None	None	None	N
H/C	0.1608	likely_benign	0.1756	benign	-0.267	Destabilizing	0.983	D	0.561	neutral	None	None	None	None	N
H/D	0.5061	ambiguous	0.4953	ambiguous	-0.893	Destabilizing	0.101	N	0.435	neutral	N	0.493601787	None	None	N
H/E	0.5529	ambiguous	0.5526	ambiguous	-0.826	Destabilizing	0.001	N	0.138	neutral	None	None	None	None	N
H/F	0.2229	likely_benign	0.2957	benign	-0.062	Destabilizing	0.002	N	0.345	neutral	None	None	None	None	N
H/G	0.3902	ambiguous	0.3797	ambiguous	-1.108	Destabilizing	0.228	N	0.405	neutral	None	None	None	None	N
H/I	0.4965	ambiguous	0.5322	ambiguous	0.022	Stabilizing	0.264	N	0.541	neutral	None	None	None	None	N
H/K	0.5504	ambiguous	0.5612	ambiguous	-0.815	Destabilizing	0.129	N	0.436	neutral	None	None	None	None	N
H/L	0.2847	likely_benign	0.3039	benign	0.022	Stabilizing	0.001	N	0.407	neutral	N	0.51315034	None	None	N
H/M	0.4656	ambiguous	0.5142	ambiguous	-0.046	Destabilizing	0.716	D	0.581	neutral	None	None	None	None	N
H/N	0.13	likely_benign	0.1339	benign	-0.767	Destabilizing	0.351	N	0.358	neutral	N	0.479864485	None	None	N
H/P	0.9719	likely_pathogenic	0.9693	pathogenic	-0.234	Destabilizing	0.523	D	0.639	neutral	N	0.476368761	None	None	N
H/Q	0.2744	likely_benign	0.3042	benign	-0.582	Destabilizing	0.213	N	0.385	neutral	N	0.462105444	None	None	N
H/R	0.294	likely_benign	0.308	benign	-1.043	Destabilizing	0.351	N	0.354	neutral	N	0.461105366	None	None	N
H/S	0.1698	likely_benign	0.1818	benign	-0.812	Destabilizing	0.012	N	0.195	neutral	None	None	None	None	N
H/T	0.228	likely_benign	0.2577	benign	-0.66	Destabilizing	0.129	N	0.416	neutral	None	None	None	None	N
H/V	0.3876	ambiguous	0.4257	ambiguous	-0.234	Destabilizing	0.129	N	0.458	neutral	None	None	None	None	N
H/W	0.5011	ambiguous	0.5619	ambiguous	-0.003	Destabilizing	0.983	D	0.559	neutral	None	None	None	None	N
H/Y	0.1089	likely_benign	0.1309	benign	0.279	Stabilizing	0.213	N	0.365	neutral	N	0.469090131	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.