TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26044	78355;78356;78357	chr2:178568002;178568001;178568000	chr2:179432729;179432728;179432727
N2AB	24403	73432;73433;73434	chr2:178568002;178568001;178568000	chr2:179432729;179432728;179432727
N2A	23476	70651;70652;70653	chr2:178568002;178568001;178568000	chr2:179432729;179432728;179432727
N2B	16979	51160;51161;51162	chr2:178568002;178568001;178568000	chr2:179432729;179432728;179432727
Novex-1	17104	51535;51536;51537	chr2:178568002;178568001;178568000	chr2:179432729;179432728;179432727
Novex-2	17171	51736;51737;51738	chr2:178568002;178568001;178568000	chr2:179432729;179432728;179432727
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-77
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.3316
• 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
I/V	rs755172743	-1.149	0.002	N	0.11	0.073	0.357519025918	gnomAD-2.1.1	3.63E-05	None	None	None	None	N	None	0	0	None	0	0	None	2.94175E-04	None	0	0	0
I/V	rs755172743	-1.149	0.002	N	0.11	0.073	0.357519025918	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.06868E-04	0
I/V	rs755172743	-1.149	0.002	N	0.11	0.073	0.357519025918	gnomAD-4.0.0	6.81793E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.20776E-04	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
I/A	0.2025	likely_benign	0.2003	benign	-1.869	Destabilizing	0.002	N	0.16	neutral	None	None	None	None	N
I/C	0.5662	likely_pathogenic	0.5726	pathogenic	-0.736	Destabilizing	0.92	D	0.357	neutral	None	None	None	None	N
I/D	0.7322	likely_pathogenic	0.7453	pathogenic	-1.684	Destabilizing	0.92	D	0.477	neutral	None	None	None	None	N
I/E	0.6265	likely_pathogenic	0.6365	pathogenic	-1.688	Destabilizing	0.85	D	0.465	neutral	None	None	None	None	N
I/F	0.2003	likely_benign	0.2194	benign	-1.413	Destabilizing	0.681	D	0.377	neutral	N	0.490158837	None	None	N
I/G	0.525	ambiguous	0.5386	ambiguous	-2.19	Highly Destabilizing	0.447	N	0.459	neutral	None	None	None	None	N
I/H	0.5473	ambiguous	0.5718	pathogenic	-1.549	Destabilizing	0.992	D	0.418	neutral	None	None	None	None	N
I/K	0.3685	ambiguous	0.3781	ambiguous	-1.321	Destabilizing	0.85	D	0.467	neutral	None	None	None	None	N
I/L	0.0669	likely_benign	0.0682	benign	-1.042	Destabilizing	0.001	N	0.079	neutral	N	0.350494879	None	None	N
I/M	0.0883	likely_benign	0.092	benign	-0.569	Destabilizing	0.81	D	0.399	neutral	N	0.490158837	None	None	N
I/N	0.2809	likely_benign	0.2955	benign	-1.021	Destabilizing	0.896	D	0.47	neutral	N	0.439767302	None	None	N
I/P	0.2717	likely_benign	0.263	benign	-1.289	Destabilizing	0.92	D	0.469	neutral	None	None	None	None	N
I/Q	0.4258	ambiguous	0.4371	ambiguous	-1.233	Destabilizing	0.92	D	0.457	neutral	None	None	None	None	N
I/R	0.3073	likely_benign	0.3241	benign	-0.667	Destabilizing	0.92	D	0.465	neutral	None	None	None	None	N
I/S	0.2792	likely_benign	0.2893	benign	-1.52	Destabilizing	0.379	N	0.389	neutral	N	0.399728834	None	None	N
I/T	0.1982	likely_benign	0.1914	benign	-1.424	Destabilizing	0.549	D	0.363	neutral	N	0.394285728	None	None	N
I/V	0.055	likely_benign	0.0543	benign	-1.289	Destabilizing	0.002	N	0.11	neutral	N	0.425974073	None	None	N
I/W	0.8014	likely_pathogenic	0.8259	pathogenic	-1.553	Destabilizing	0.992	D	0.482	neutral	None	None	None	None	N
I/Y	0.5548	ambiguous	0.5895	pathogenic	-1.36	Destabilizing	0.92	D	0.391	neutral	None	None	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.