TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21770	65533;65534;65535	chr2:178583874;178583873;178583872	chr2:179448601;179448600;179448599
N2AB	20129	60610;60611;60612	chr2:178583874;178583873;178583872	chr2:179448601;179448600;179448599
N2A	19202	57829;57830;57831	chr2:178583874;178583873;178583872	chr2:179448601;179448600;179448599
N2B	12705	38338;38339;38340	chr2:178583874;178583873;178583872	chr2:179448601;179448600;179448599
Novex-1	12830	38713;38714;38715	chr2:178583874;178583873;178583872	chr2:179448601;179448600;179448599
Novex-2	12897	38914;38915;38916	chr2:178583874;178583873;178583872	chr2:179448601;179448600;179448599
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-46
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.2539
• 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
T/S	None	None	0.001	N	0.195	0.149	0.143124449307	gnomAD-4.0.0	1.63093E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.93748E-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
T/A	0.3733	ambiguous	0.2989	benign	-0.712	Destabilizing	0.004	N	0.218	neutral	N	0.477755248	None	None	N
T/C	0.7689	likely_pathogenic	0.6774	pathogenic	-0.47	Destabilizing	0.909	D	0.521	neutral	None	None	None	None	N
T/D	0.6246	likely_pathogenic	0.5785	pathogenic	-0.278	Destabilizing	0.396	N	0.495	neutral	None	None	None	None	N
T/E	0.7397	likely_pathogenic	0.7206	pathogenic	-0.303	Destabilizing	0.157	N	0.494	neutral	None	None	None	None	N
T/F	0.8426	likely_pathogenic	0.797	pathogenic	-0.909	Destabilizing	0.726	D	0.585	neutral	None	None	None	None	N
T/G	0.3281	likely_benign	0.2725	benign	-0.936	Destabilizing	0.157	N	0.529	neutral	None	None	None	None	N
T/H	0.6376	likely_pathogenic	0.5611	ambiguous	-1.263	Destabilizing	0.909	D	0.563	neutral	None	None	None	None	N
T/I	0.9204	likely_pathogenic	0.8889	pathogenic	-0.218	Destabilizing	0.497	N	0.515	neutral	N	0.513914533	None	None	N
T/K	0.5846	likely_pathogenic	0.5598	ambiguous	-0.674	Destabilizing	0.157	N	0.495	neutral	None	None	None	None	N
T/L	0.5288	ambiguous	0.4682	ambiguous	-0.218	Destabilizing	0.272	N	0.505	neutral	None	None	None	None	N
T/M	0.3746	ambiguous	0.3276	benign	0.114	Stabilizing	0.968	D	0.521	neutral	None	None	None	None	N
T/N	0.2534	likely_benign	0.2165	benign	-0.584	Destabilizing	0.331	N	0.497	neutral	N	0.471599502	None	None	N
T/P	0.8176	likely_pathogenic	0.8291	pathogenic	-0.351	Destabilizing	0.497	N	0.521	neutral	N	0.513914533	None	None	N
T/Q	0.5172	ambiguous	0.4963	ambiguous	-0.82	Destabilizing	0.567	D	0.522	neutral	None	None	None	None	N
T/R	0.5444	ambiguous	0.5282	ambiguous	-0.391	Destabilizing	0.567	D	0.513	neutral	None	None	None	None	N
T/S	0.1533	likely_benign	0.1235	benign	-0.833	Destabilizing	0.001	N	0.195	neutral	N	0.510400823	None	None	N
T/V	0.8036	likely_pathogenic	0.7513	pathogenic	-0.351	Destabilizing	0.272	N	0.506	neutral	None	None	None	None	N
T/W	0.9305	likely_pathogenic	0.916	pathogenic	-0.832	Destabilizing	0.968	D	0.639	neutral	None	None	None	None	N
T/Y	0.8217	likely_pathogenic	0.7608	pathogenic	-0.592	Destabilizing	0.726	D	0.58	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.