TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2876	8851;8852;8853	chr2:178770075;178770074;178770073	chr2:179634802;179634801;179634800
N2AB	2876	8851;8852;8853	chr2:178770075;178770074;178770073	chr2:179634802;179634801;179634800
N2A	2876	8851;8852;8853	chr2:178770075;178770074;178770073	chr2:179634802;179634801;179634800
N2B	2830	8713;8714;8715	chr2:178770075;178770074;178770073	chr2:179634802;179634801;179634800
Novex-1	2830	8713;8714;8715	chr2:178770075;178770074;178770073	chr2:179634802;179634801;179634800
Novex-2	2830	8713;8714;8715	chr2:178770075;178770074;178770073	chr2:179634802;179634801;179634800
Novex-3	2876	8851;8852;8853	chr2:178770075;178770074;178770073	chr2:179634802;179634801;179634800

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-18
• Domain position: 82
• Structural Position: 173
• Q(SASA): 0.3034
• 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
K/E	None	None	0.959	N	0.557	0.325	0.317378411342	gnomAD-4.0.0	6.84061E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9929E-07	0	0
K/Q	None	None	0.996	N	0.617	0.338	0.223847106136	gnomAD-4.0.0	6.84061E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15931E-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
K/A	0.5964	likely_pathogenic	0.5806	pathogenic	-0.798	Destabilizing	0.863	D	0.471	neutral	None	None	None	None	N
K/C	0.7933	likely_pathogenic	0.7894	pathogenic	-0.724	Destabilizing	0.999	D	0.556	neutral	None	None	None	None	N
K/D	0.8348	likely_pathogenic	0.8061	pathogenic	0.106	Stabilizing	0.969	D	0.618	neutral	None	None	None	None	N
K/E	0.4241	ambiguous	0.3666	ambiguous	0.256	Stabilizing	0.959	D	0.557	neutral	N	0.497298163	None	None	N
K/F	0.8763	likely_pathogenic	0.8603	pathogenic	-0.369	Destabilizing	0.991	D	0.585	neutral	None	None	None	None	N
K/G	0.7664	likely_pathogenic	0.7618	pathogenic	-1.184	Destabilizing	0.969	D	0.576	neutral	None	None	None	None	N
K/H	0.3385	likely_benign	0.3322	benign	-1.288	Destabilizing	0.999	D	0.586	neutral	None	None	None	None	N
K/I	0.5534	ambiguous	0.5206	ambiguous	0.218	Stabilizing	0.134	N	0.328	neutral	D	0.593328632	None	None	N
K/L	0.5342	ambiguous	0.5161	ambiguous	0.218	Stabilizing	0.759	D	0.451	neutral	None	None	None	None	N
K/M	0.3639	ambiguous	0.336	benign	0.005	Stabilizing	0.991	D	0.613	neutral	None	None	None	None	N
K/N	0.562	ambiguous	0.5358	ambiguous	-0.491	Destabilizing	0.959	D	0.606	neutral	N	0.504616756	None	None	N
K/P	0.9664	likely_pathogenic	0.9578	pathogenic	-0.092	Destabilizing	0.997	D	0.624	neutral	None	None	None	None	N
K/Q	0.1999	likely_benign	0.1895	benign	-0.477	Destabilizing	0.996	D	0.617	neutral	N	0.497118912	None	None	N
K/R	0.0818	likely_benign	0.0868	benign	-0.457	Destabilizing	0.959	D	0.543	neutral	N	0.496239465	None	None	N
K/S	0.5961	likely_pathogenic	0.5806	pathogenic	-1.252	Destabilizing	0.759	D	0.561	neutral	None	None	None	None	N
K/T	0.2851	likely_benign	0.2583	benign	-0.875	Destabilizing	0.061	N	0.232	neutral	N	0.463343052	None	None	N
K/V	0.457	ambiguous	0.4354	ambiguous	-0.092	Destabilizing	0.17	N	0.281	neutral	None	None	None	None	N
K/W	0.8548	likely_pathogenic	0.8495	pathogenic	-0.2	Destabilizing	0.999	D	0.569	neutral	None	None	None	None	N
K/Y	0.7424	likely_pathogenic	0.7255	pathogenic	0.065	Stabilizing	0.997	D	0.577	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.