TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27555	82888;82889;82890	chr2:178563469;178563468;178563467	chr2:179428196;179428195;179428194
N2AB	25914	77965;77966;77967	chr2:178563469;178563468;178563467	chr2:179428196;179428195;179428194
N2A	24987	75184;75185;75186	chr2:178563469;178563468;178563467	chr2:179428196;179428195;179428194
N2B	18490	55693;55694;55695	chr2:178563469;178563468;178563467	chr2:179428196;179428195;179428194
Novex-1	18615	56068;56069;56070	chr2:178563469;178563468;178563467	chr2:179428196;179428195;179428194
Novex-2	18682	56269;56270;56271	chr2:178563469;178563468;178563467	chr2:179428196;179428195;179428194
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-88
• Domain position: 87
• Structural Position: 120
• Q(SASA): 0.381
• 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
P/A	None	None	0.338	N	0.558	0.202	0.194818534648	gnomAD-4.0.0	6.84248E-07	None	None	None	None	I	None	2.98793E-05	0	None	0	0	None	0	0	0	0	0
P/L	rs1704434305	None	0.338	N	0.651	0.298	0.570825458115	gnomAD-4.0.0	1.59147E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8585E-06	0	0
P/S	rs1704435200	None	0.013	N	0.37	0.256	0.193865811164	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	0	0	0	0	None	1.8843E-04	0	0	0	0
P/S	rs1704435200	None	0.013	N	0.37	0.256	0.193865811164	gnomAD-4.0.0	3.09888E-06	None	None	None	None	I	None	0	0	None	0	0	None	7.81104E-05	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
P/A	0.0967	likely_benign	0.0934	benign	-1.392	Destabilizing	0.338	N	0.558	neutral	N	0.474113808	None	None	I
P/C	0.4641	ambiguous	0.4343	ambiguous	-0.842	Destabilizing	0.991	D	0.761	deleterious	None	None	None	None	I
P/D	0.6735	likely_pathogenic	0.7203	pathogenic	-1.284	Destabilizing	0.826	D	0.549	neutral	None	None	None	None	I
P/E	0.4861	ambiguous	0.536	ambiguous	-1.346	Destabilizing	0.826	D	0.555	neutral	None	None	None	None	I
P/F	0.3541	ambiguous	0.3483	ambiguous	-1.257	Destabilizing	0.01	N	0.597	neutral	None	None	None	None	I
P/G	0.416	ambiguous	0.4504	ambiguous	-1.635	Destabilizing	0.404	N	0.569	neutral	None	None	None	None	I
P/H	0.2689	likely_benign	0.287	benign	-1.156	Destabilizing	0.988	D	0.698	prob.neutral	N	0.521909341	None	None	I
P/I	0.3062	likely_benign	0.2882	benign	-0.848	Destabilizing	0.704	D	0.713	prob.delet.	None	None	None	None	I
P/K	0.4623	ambiguous	0.4815	ambiguous	-1.133	Destabilizing	0.826	D	0.551	neutral	None	None	None	None	I
P/L	0.134	likely_benign	0.1263	benign	-0.848	Destabilizing	0.338	N	0.651	neutral	N	0.503004938	None	None	I
P/M	0.3126	likely_benign	0.2958	benign	-0.577	Destabilizing	0.973	D	0.701	prob.neutral	None	None	None	None	I
P/N	0.4823	ambiguous	0.5161	ambiguous	-0.815	Destabilizing	0.826	D	0.648	neutral	None	None	None	None	I
P/Q	0.2756	likely_benign	0.2956	benign	-1.093	Destabilizing	0.826	D	0.609	neutral	None	None	None	None	I
P/R	0.3059	likely_benign	0.3256	benign	-0.515	Destabilizing	0.782	D	0.683	prob.neutral	N	0.520895383	None	None	I
P/S	0.1968	likely_benign	0.2112	benign	-1.244	Destabilizing	0.013	N	0.37	neutral	N	0.502030659	None	None	I
P/T	0.1723	likely_benign	0.1728	benign	-1.214	Destabilizing	0.338	N	0.504	neutral	N	0.509792567	None	None	I
P/V	0.2115	likely_benign	0.2006	benign	-0.995	Destabilizing	0.704	D	0.603	neutral	None	None	None	None	I
P/W	0.5352	ambiguous	0.5474	ambiguous	-1.352	Destabilizing	0.973	D	0.747	deleterious	None	None	None	None	I
P/Y	0.3514	ambiguous	0.3456	ambiguous	-1.104	Destabilizing	0.704	D	0.736	prob.delet.	None	None	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.