TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27377	82354;82355;82356	chr2:178564003;178564002;178564001	chr2:179428730;179428729;179428728
N2AB	25736	77431;77432;77433	chr2:178564003;178564002;178564001	chr2:179428730;179428729;179428728
N2A	24809	74650;74651;74652	chr2:178564003;178564002;178564001	chr2:179428730;179428729;179428728
N2B	18312	55159;55160;55161	chr2:178564003;178564002;178564001	chr2:179428730;179428729;179428728
Novex-1	18437	55534;55535;55536	chr2:178564003;178564002;178564001	chr2:179428730;179428729;179428728
Novex-2	18504	55735;55736;55737	chr2:178564003;178564002;178564001	chr2:179428730;179428729;179428728
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-87
• Domain position: 9
• Structural Position: 9
• Q(SASA): 0.1256
• 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
L/P	None	None	0.056	N	0.653	0.34	0.664596153488	gnomAD-4.0.0	1.36847E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99505E-07	0	1.65673E-05

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
L/A	0.8502	likely_pathogenic	0.823	pathogenic	-2.35	Highly Destabilizing	0.916	D	0.682	prob.neutral	None	None	None	None	N
L/C	0.8193	likely_pathogenic	0.815	pathogenic	-1.657	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	N
L/D	0.9983	likely_pathogenic	0.9978	pathogenic	-2.701	Highly Destabilizing	0.987	D	0.807	deleterious	None	None	None	None	N
L/E	0.9865	likely_pathogenic	0.9835	pathogenic	-2.465	Highly Destabilizing	0.975	D	0.812	deleterious	None	None	None	None	N
L/F	0.4817	ambiguous	0.4963	ambiguous	-1.319	Destabilizing	0.987	D	0.769	deleterious	None	None	None	None	N
L/G	0.9768	likely_pathogenic	0.9704	pathogenic	-2.896	Highly Destabilizing	0.975	D	0.815	deleterious	None	None	None	None	N
L/H	0.9792	likely_pathogenic	0.9759	pathogenic	-2.457	Highly Destabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
L/I	0.1116	likely_benign	0.1107	benign	-0.773	Destabilizing	0.253	N	0.428	neutral	None	None	None	None	N
L/K	0.9839	likely_pathogenic	0.9808	pathogenic	-1.756	Destabilizing	0.975	D	0.777	deleterious	None	None	None	None	N
L/M	0.201	likely_benign	0.2063	benign	-0.851	Destabilizing	0.983	D	0.703	prob.neutral	N	0.48193012	None	None	N
L/N	0.9885	likely_pathogenic	0.9847	pathogenic	-2.121	Highly Destabilizing	0.987	D	0.811	deleterious	None	None	None	None	N
L/P	0.9158	likely_pathogenic	0.9007	pathogenic	-1.28	Destabilizing	0.056	N	0.653	neutral	N	0.506984877	None	None	N
L/Q	0.9555	likely_pathogenic	0.9463	pathogenic	-1.948	Destabilizing	0.983	D	0.774	deleterious	N	0.497262898	None	None	N
L/R	0.9715	likely_pathogenic	0.967	pathogenic	-1.584	Destabilizing	0.983	D	0.759	deleterious	N	0.493642047	None	None	N
L/S	0.9709	likely_pathogenic	0.9615	pathogenic	-2.782	Highly Destabilizing	0.975	D	0.781	deleterious	None	None	None	None	N
L/T	0.9014	likely_pathogenic	0.875	pathogenic	-2.401	Highly Destabilizing	0.975	D	0.759	deleterious	None	None	None	None	N
L/V	0.1171	likely_benign	0.1168	benign	-1.28	Destabilizing	0.63	D	0.719	prob.delet.	N	0.447509712	None	None	N
L/W	0.9099	likely_pathogenic	0.9112	pathogenic	-1.739	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
L/Y	0.9398	likely_pathogenic	0.9359	pathogenic	-1.418	Destabilizing	0.996	D	0.709	prob.delet.	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.