TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8692	26299;26300;26301	chr2:178715112;178715111;178715110	chr2:179579839;179579838;179579837
N2AB	8375	25348;25349;25350	chr2:178715112;178715111;178715110	chr2:179579839;179579838;179579837
N2A	7448	22567;22568;22569	chr2:178715112;178715111;178715110	chr2:179579839;179579838;179579837
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: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-72
• Domain position: 50
• Structural Position: 125
• Q(SASA): 0.5217
• 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
M/I	rs1041074010	-0.151	0.001	N	0.073	0.149	0.393159880135	gnomAD-4.0.0	1.16321E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.5292E-05	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
M/A	0.4155	ambiguous	0.317	benign	-1.413	Destabilizing	0.005	N	0.157	neutral	None	None	None	None	N
M/C	0.7763	likely_pathogenic	0.7256	pathogenic	-0.808	Destabilizing	0.962	D	0.421	neutral	None	None	None	None	N
M/D	0.82	likely_pathogenic	0.7394	pathogenic	-0.189	Destabilizing	0.683	D	0.567	neutral	None	None	None	None	N
M/E	0.5769	likely_pathogenic	0.4826	ambiguous	-0.195	Destabilizing	0.3	N	0.521	neutral	None	None	None	None	N
M/F	0.3158	likely_benign	0.2444	benign	-0.645	Destabilizing	0.142	N	0.265	neutral	None	None	None	None	N
M/G	0.6465	likely_pathogenic	0.5442	ambiguous	-1.685	Destabilizing	0.423	N	0.439	neutral	None	None	None	None	N
M/H	0.4411	ambiguous	0.365	ambiguous	-0.744	Destabilizing	0.97	D	0.474	neutral	None	None	None	None	N
M/I	0.3803	ambiguous	0.284	benign	-0.739	Destabilizing	0.001	N	0.073	neutral	N	0.422235626	None	None	N
M/K	0.2288	likely_benign	0.1822	benign	-0.198	Destabilizing	0.331	N	0.415	neutral	N	0.453939826	None	None	N
M/L	0.1461	likely_benign	0.1185	benign	-0.739	Destabilizing	None	N	0.061	neutral	N	0.398203973	None	None	N
M/N	0.4939	ambiguous	0.397	ambiguous	0.019	Stabilizing	0.883	D	0.561	neutral	None	None	None	None	N
M/P	0.9529	likely_pathogenic	0.9263	pathogenic	-0.936	Destabilizing	0.683	D	0.553	neutral	None	None	None	None	N
M/Q	0.2577	likely_benign	0.2227	benign	-0.114	Destabilizing	0.749	D	0.34	neutral	None	None	None	None	N
M/R	0.2364	likely_benign	0.1893	benign	0.305	Stabilizing	0.683	D	0.479	neutral	N	0.448688722	None	None	N
M/S	0.3586	ambiguous	0.2731	benign	-0.569	Destabilizing	0.423	N	0.357	neutral	None	None	None	None	N
M/T	0.1994	likely_benign	0.146	benign	-0.465	Destabilizing	0.249	N	0.333	neutral	N	0.396835749	None	None	N
M/V	0.1225	likely_benign	0.1031	benign	-0.936	Destabilizing	0.002	N	0.079	neutral	N	0.409343687	None	None	N
M/W	0.6813	likely_pathogenic	0.6104	pathogenic	-0.544	Destabilizing	0.998	D	0.407	neutral	None	None	None	None	N
M/Y	0.5925	likely_pathogenic	0.5094	ambiguous	-0.537	Destabilizing	0.8	D	0.494	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.