TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21812	65659;65660;65661	chr2:178583748;178583747;178583746	chr2:179448475;179448474;179448473
N2AB	20171	60736;60737;60738	chr2:178583748;178583747;178583746	chr2:179448475;179448474;179448473
N2A	19244	57955;57956;57957	chr2:178583748;178583747;178583746	chr2:179448475;179448474;179448473
N2B	12747	38464;38465;38466	chr2:178583748;178583747;178583746	chr2:179448475;179448474;179448473
Novex-1	12872	38839;38840;38841	chr2:178583748;178583747;178583746	chr2:179448475;179448474;179448473
Novex-2	12939	39040;39041;39042	chr2:178583748;178583747;178583746	chr2:179448475;179448474;179448473
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: Fn3-46
• Domain position: 56
• Structural Position: 74
• Q(SASA): 0.4871
• 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/N	rs267599042	0.009	0.189	N	0.163	0.079	0.124217242631	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.97E-06	0
H/N	rs267599042	0.009	0.189	N	0.163	0.079	0.124217242631	gnomAD-4.0.0	3.19077E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86405E-06	0	3.03288E-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	0.1729	likely_benign	0.1576	benign	0.384	Stabilizing	0.028	N	0.187	neutral	None	None	None	None	N
H/C	0.1684	likely_benign	0.1438	benign	0.861	Stabilizing	0.942	D	0.356	neutral	None	None	None	None	N
H/D	0.1884	likely_benign	0.1775	benign	-0.091	Destabilizing	0.189	N	0.234	neutral	N	0.41146598	None	None	N
H/E	0.2645	likely_benign	0.2378	benign	-0.061	Destabilizing	0.063	N	0.099	neutral	None	None	None	None	N
H/F	0.2476	likely_benign	0.2241	benign	1.088	Stabilizing	0.134	N	0.293	neutral	None	None	None	None	N
H/G	0.1754	likely_benign	0.1691	benign	0.09	Stabilizing	0.063	N	0.232	neutral	None	None	None	None	N
H/I	0.2539	likely_benign	0.2223	benign	1.137	Stabilizing	0.134	N	0.254	neutral	None	None	None	None	N
H/K	0.2802	likely_benign	0.231	benign	0.291	Stabilizing	0.063	N	0.234	neutral	None	None	None	None	N
H/L	0.0998	likely_benign	0.0979	benign	1.137	Stabilizing	None	N	0.119	neutral	N	0.413372922	None	None	N
H/M	0.3465	ambiguous	0.3134	benign	0.87	Stabilizing	0.012	N	0.081	neutral	None	None	None	None	N
H/N	0.0834	likely_benign	0.0811	benign	0.291	Stabilizing	0.189	N	0.163	neutral	N	0.45431268	None	None	N
H/P	0.1258	likely_benign	0.1127	benign	0.912	Stabilizing	0.534	D	0.354	neutral	N	0.455179472	None	None	N
H/Q	0.1345	likely_benign	0.1194	benign	0.412	Stabilizing	0.003	N	0.039	neutral	N	0.380836429	None	None	N
H/R	0.1335	likely_benign	0.1165	benign	-0.376	Destabilizing	0.189	N	0.147	neutral	N	0.456219622	None	None	N
H/S	0.1302	likely_benign	0.1226	benign	0.459	Stabilizing	0.004	N	0.082	neutral	None	None	None	None	N
H/T	0.1897	likely_benign	0.1713	benign	0.587	Stabilizing	0.001	N	0.084	neutral	None	None	None	None	N
H/V	0.1986	likely_benign	0.1726	benign	0.912	Stabilizing	0.063	N	0.216	neutral	None	None	None	None	N
H/W	0.3303	likely_benign	0.3274	benign	1.062	Stabilizing	0.842	D	0.321	neutral	None	None	None	None	N
H/Y	0.0909	likely_benign	0.089	benign	1.335	Stabilizing	0.001	N	0.065	neutral	N	0.415527792	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.