TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27063	81412;81413;81414	chr2:178564945;178564944;178564943	chr2:179429672;179429671;179429670
N2AB	25422	76489;76490;76491	chr2:178564945;178564944;178564943	chr2:179429672;179429671;179429670
N2A	24495	73708;73709;73710	chr2:178564945;178564944;178564943	chr2:179429672;179429671;179429670
N2B	17998	54217;54218;54219	chr2:178564945;178564944;178564943	chr2:179429672;179429671;179429670
Novex-1	18123	54592;54593;54594	chr2:178564945;178564944;178564943	chr2:179429672;179429671;179429670
Novex-2	18190	54793;54794;54795	chr2:178564945;178564944;178564943	chr2:179429672;179429671;179429670
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-84
• Domain position: 92
• Structural Position: 126
• Q(SASA): 0.3301
• 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
A/E	rs1705140581	None	0.03	N	0.482	0.141	0.283371740733	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
A/C	0.304	likely_benign	0.3012	benign	-0.776	Destabilizing	0.685	D	0.485	neutral	None	None	None	None	N
A/D	0.3357	likely_benign	0.3546	ambiguous	-0.673	Destabilizing	0.039	N	0.583	neutral	None	None	None	None	N
A/E	0.2725	likely_benign	0.2792	benign	-0.738	Destabilizing	0.03	N	0.482	neutral	N	0.428952876	None	None	N
A/F	0.4019	ambiguous	0.3649	ambiguous	-0.789	Destabilizing	0.366	N	0.621	neutral	None	None	None	None	N
A/G	0.1461	likely_benign	0.1417	benign	-0.79	Destabilizing	0.012	N	0.424	neutral	N	0.469212283	None	None	N
A/H	0.3949	ambiguous	0.4036	ambiguous	-0.799	Destabilizing	0.366	N	0.605	neutral	None	None	None	None	N
A/I	0.2607	likely_benign	0.2334	benign	-0.229	Destabilizing	0.221	N	0.547	neutral	None	None	None	None	N
A/K	0.4901	ambiguous	0.4975	ambiguous	-0.956	Destabilizing	0.039	N	0.484	neutral	None	None	None	None	N
A/L	0.1902	likely_benign	0.175	benign	-0.229	Destabilizing	0.075	N	0.483	neutral	None	None	None	None	N
A/M	0.2323	likely_benign	0.2099	benign	-0.335	Destabilizing	0.869	D	0.5	neutral	None	None	None	None	N
A/N	0.2215	likely_benign	0.2272	benign	-0.66	Destabilizing	0.001	N	0.357	neutral	None	None	None	None	N
A/P	0.062	likely_benign	0.0612	benign	-0.31	Destabilizing	None	N	0.179	neutral	N	0.362130451	None	None	N
A/Q	0.2995	likely_benign	0.3002	benign	-0.834	Destabilizing	0.221	N	0.544	neutral	None	None	None	None	N
A/R	0.4561	ambiguous	0.4736	ambiguous	-0.555	Destabilizing	0.221	N	0.549	neutral	None	None	None	None	N
A/S	0.0925	likely_benign	0.0974	benign	-0.973	Destabilizing	None	N	0.223	neutral	N	0.43039567	None	None	N
A/T	0.0963	likely_benign	0.0924	benign	-0.938	Destabilizing	0.03	N	0.452	neutral	N	0.461737298	None	None	N
A/V	0.1436	likely_benign	0.1326	benign	-0.31	Destabilizing	0.058	N	0.434	neutral	N	0.443612897	None	None	N
A/W	0.7163	likely_pathogenic	0.7184	pathogenic	-1.056	Destabilizing	0.869	D	0.702	prob.delet.	None	None	None	None	N
A/Y	0.4324	ambiguous	0.4348	ambiguous	-0.664	Destabilizing	0.366	N	0.621	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.