TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23554	70885;70886;70887	chr2:178575472;178575471;178575470	chr2:179440199;179440198;179440197
N2AB	21913	65962;65963;65964	chr2:178575472;178575471;178575470	chr2:179440199;179440198;179440197
N2A	20986	63181;63182;63183	chr2:178575472;178575471;178575470	chr2:179440199;179440198;179440197
N2B	14489	43690;43691;43692	chr2:178575472;178575471;178575470	chr2:179440199;179440198;179440197
Novex-1	14614	44065;44066;44067	chr2:178575472;178575471;178575470	chr2:179440199;179440198;179440197
Novex-2	14681	44266;44267;44268	chr2:178575472;178575471;178575470	chr2:179440199;179440198;179440197
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-59
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.2563
• 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
P/S	None	None	0.309	N	0.447	0.135	0.166414681773	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
P/A	0.1217	likely_benign	0.1334	benign	-1.798	Destabilizing	0.028	N	0.22	neutral	N	0.397171318	None	None	N
P/C	0.5655	likely_pathogenic	0.6202	pathogenic	-1.212	Destabilizing	0.996	D	0.557	neutral	None	None	None	None	N
P/D	0.5945	likely_pathogenic	0.5997	pathogenic	-1.839	Destabilizing	0.59	D	0.436	neutral	None	None	None	None	N
P/E	0.342	ambiguous	0.3523	ambiguous	-1.76	Destabilizing	0.742	D	0.437	neutral	None	None	None	None	N
P/F	0.6549	likely_pathogenic	0.677	pathogenic	-1.238	Destabilizing	0.984	D	0.569	neutral	None	None	None	None	N
P/G	0.3403	ambiguous	0.3679	ambiguous	-2.205	Highly Destabilizing	0.373	N	0.493	neutral	None	None	None	None	N
P/H	0.333	likely_benign	0.3503	ambiguous	-1.725	Destabilizing	0.939	D	0.527	neutral	N	0.453179316	None	None	N
P/I	0.3954	ambiguous	0.4157	ambiguous	-0.739	Destabilizing	0.91	D	0.562	neutral	None	None	None	None	N
P/K	0.4175	ambiguous	0.4398	ambiguous	-1.563	Destabilizing	0.742	D	0.437	neutral	None	None	None	None	N
P/L	0.1536	likely_benign	0.1665	benign	-0.739	Destabilizing	0.684	D	0.524	neutral	N	0.404444007	None	None	N
P/M	0.3385	likely_benign	0.3663	ambiguous	-0.583	Destabilizing	0.996	D	0.522	neutral	None	None	None	None	N
P/N	0.3853	ambiguous	0.4206	ambiguous	-1.491	Destabilizing	0.009	N	0.37	neutral	None	None	None	None	N
P/Q	0.2154	likely_benign	0.2319	benign	-1.561	Destabilizing	0.91	D	0.503	neutral	None	None	None	None	N
P/R	0.3214	likely_benign	0.3413	ambiguous	-1.089	Destabilizing	0.884	D	0.546	neutral	N	0.378412199	None	None	N
P/S	0.1905	likely_benign	0.2098	benign	-2.055	Highly Destabilizing	0.309	N	0.447	neutral	N	0.363055957	None	None	N
P/T	0.1326	likely_benign	0.1443	benign	-1.85	Destabilizing	0.012	N	0.198	neutral	N	0.337448224	None	None	N
P/V	0.2539	likely_benign	0.2718	benign	-1.059	Destabilizing	0.742	D	0.508	neutral	None	None	None	None	N
P/W	0.7808	likely_pathogenic	0.7897	pathogenic	-1.526	Destabilizing	0.996	D	0.646	neutral	None	None	None	None	N
P/Y	0.5903	likely_pathogenic	0.6115	pathogenic	-1.212	Destabilizing	0.984	D	0.568	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.