TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29491	88696;88697;88698	chr2:178554988;178554987;178554986	chr2:179419715;179419714;179419713
N2AB	27850	83773;83774;83775	chr2:178554988;178554987;178554986	chr2:179419715;179419714;179419713
N2A	26923	80992;80993;80994	chr2:178554988;178554987;178554986	chr2:179419715;179419714;179419713
N2B	20426	61501;61502;61503	chr2:178554988;178554987;178554986	chr2:179419715;179419714;179419713
Novex-1	20551	61876;61877;61878	chr2:178554988;178554987;178554986	chr2:179419715;179419714;179419713
Novex-2	20618	62077;62078;62079	chr2:178554988;178554987;178554986	chr2:179419715;179419714;179419713
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-146
• Domain position: 48
• Structural Position: 127
• Q(SASA): 0.5767
• 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
N/K	None	None	0.801	N	0.403	0.189	0.187945064343	gnomAD-4.0.0	6.84259E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15937E-05	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
N/A	0.4654	ambiguous	0.4548	ambiguous	-0.648	Destabilizing	0.525	D	0.539	neutral	None	None	None	None	N
N/C	0.4659	ambiguous	0.4911	ambiguous	0.223	Stabilizing	0.998	D	0.591	neutral	None	None	None	None	N
N/D	0.2259	likely_benign	0.2076	benign	0.149	Stabilizing	0.801	D	0.384	neutral	D	0.527517651	None	None	N
N/E	0.5781	likely_pathogenic	0.5261	ambiguous	0.192	Stabilizing	0.842	D	0.373	neutral	None	None	None	None	N
N/F	0.7586	likely_pathogenic	0.733	pathogenic	-0.672	Destabilizing	0.974	D	0.599	neutral	None	None	None	None	N
N/G	0.547	ambiguous	0.5373	ambiguous	-0.927	Destabilizing	0.525	D	0.404	neutral	None	None	None	None	N
N/H	0.1965	likely_benign	0.1936	benign	-0.779	Destabilizing	0.012	N	0.226	neutral	N	0.504699507	None	None	N
N/I	0.3765	ambiguous	0.3497	ambiguous	0.028	Stabilizing	0.934	D	0.591	neutral	N	0.495518606	None	None	N
N/K	0.5225	ambiguous	0.4576	ambiguous	0.042	Stabilizing	0.801	D	0.403	neutral	N	0.518492736	None	None	N
N/L	0.4784	ambiguous	0.4502	ambiguous	0.028	Stabilizing	0.842	D	0.532	neutral	None	None	None	None	N
N/M	0.4471	ambiguous	0.4256	ambiguous	0.394	Stabilizing	0.998	D	0.581	neutral	None	None	None	None	N
N/P	0.8226	likely_pathogenic	0.8186	pathogenic	-0.168	Destabilizing	0.974	D	0.571	neutral	None	None	None	None	N
N/Q	0.5227	ambiguous	0.4987	ambiguous	-0.455	Destabilizing	0.974	D	0.511	neutral	None	None	None	None	N
N/R	0.6175	likely_pathogenic	0.5716	pathogenic	0.002	Stabilizing	0.842	D	0.492	neutral	None	None	None	None	N
N/S	0.1503	likely_benign	0.1594	benign	-0.449	Destabilizing	0.051	N	0.225	neutral	N	0.493154362	None	None	N
N/T	0.1867	likely_benign	0.1834	benign	-0.217	Destabilizing	0.051	N	0.239	neutral	N	0.460639298	None	None	N
N/V	0.4071	ambiguous	0.3852	ambiguous	-0.168	Destabilizing	0.842	D	0.565	neutral	None	None	None	None	N
N/W	0.8811	likely_pathogenic	0.8666	pathogenic	-0.499	Destabilizing	0.998	D	0.62	neutral	None	None	None	None	N
N/Y	0.2288	likely_benign	0.2151	benign	-0.274	Destabilizing	0.934	D	0.575	neutral	N	0.487756698	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.