TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7375	22348;22349;22350	chr2:178722776;178722775;178722774	chr2:179587503;179587502;179587501
N2AB	7058	21397;21398;21399	chr2:178722776;178722775;178722774	chr2:179587503;179587502;179587501
N2A	6131	18616;18617;18618	chr2:178722776;178722775;178722774	chr2:179587503;179587502;179587501
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: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-58
• Domain position: 53
• Structural Position: 131
• Q(SASA): 0.8604
• 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
N/K	rs750961839	0.532	0.028	N	0.12	0.123	0.0716867268079	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
N/K	rs750961839	0.532	0.028	N	0.12	0.123	0.0716867268079	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
N/K	rs750961839	0.532	0.028	N	0.12	0.123	0.0716867268079	gnomAD-4.0.0	6.57774E-06	None	None	None	None	I	None	2.41488E-05	0	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
N/A	0.3249	likely_benign	0.5379	ambiguous	-0.117	Destabilizing	0.068	N	0.274	neutral	None	None	None	None	I
N/C	0.559	ambiguous	0.7377	pathogenic	0.17	Stabilizing	0.994	D	0.219	neutral	None	None	None	None	I
N/D	0.0944	likely_benign	0.1695	benign	0.183	Stabilizing	0.001	N	0.105	neutral	N	0.420631676	None	None	I
N/E	0.3727	ambiguous	0.6175	pathogenic	0.123	Stabilizing	0.272	N	0.263	neutral	None	None	None	None	I
N/F	0.8182	likely_pathogenic	0.9313	pathogenic	-0.712	Destabilizing	0.993	D	0.213	neutral	None	None	None	None	I
N/G	0.2314	likely_benign	0.3653	ambiguous	-0.214	Destabilizing	0.006	N	0.109	neutral	None	None	None	None	I
N/H	0.1387	likely_benign	0.2177	benign	-0.228	Destabilizing	0.976	D	0.227	neutral	N	0.501884835	None	None	I
N/I	0.6881	likely_pathogenic	0.8933	pathogenic	0.04	Stabilizing	0.931	D	0.241	neutral	N	0.459744265	None	None	I
N/K	0.2858	likely_benign	0.5376	ambiguous	0.161	Stabilizing	0.028	N	0.12	neutral	N	0.472831365	None	None	I
N/L	0.5407	ambiguous	0.7452	pathogenic	0.04	Stabilizing	0.837	D	0.312	neutral	None	None	None	None	I
N/M	0.6223	likely_pathogenic	0.8176	pathogenic	0.13	Stabilizing	0.995	D	0.197	neutral	None	None	None	None	I
N/P	0.8542	likely_pathogenic	0.9271	pathogenic	0.011	Stabilizing	0.794	D	0.272	neutral	None	None	None	None	I
N/Q	0.3508	ambiguous	0.553	ambiguous	-0.271	Destabilizing	0.717	D	0.25	neutral	None	None	None	None	I
N/R	0.3203	likely_benign	0.5415	ambiguous	0.216	Stabilizing	0.772	D	0.216	neutral	None	None	None	None	I
N/S	0.0976	likely_benign	0.1315	benign	-0.05	Destabilizing	0.146	N	0.285	neutral	N	0.477890468	None	None	I
N/T	0.314	likely_benign	0.5085	ambiguous	0.01	Stabilizing	0.388	N	0.199	neutral	N	0.493726712	None	None	I
N/V	0.6127	likely_pathogenic	0.8355	pathogenic	0.011	Stabilizing	0.601	D	0.301	neutral	None	None	None	None	I
N/W	0.8674	likely_pathogenic	0.955	pathogenic	-0.833	Destabilizing	0.998	D	0.342	neutral	None	None	None	None	I
N/Y	0.3116	likely_benign	0.5032	ambiguous	-0.506	Destabilizing	0.991	D	0.211	neutral	N	0.453819236	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.