TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10013	30262;30263;30264	chr2:178704333;178704332;178704331	chr2:179569060;179569059;179569058
N2AB	9696	29311;29312;29313	chr2:178704333;178704332;178704331	chr2:179569060;179569059;179569058
N2A	8769	26530;26531;26532	chr2:178704333;178704332;178704331	chr2:179569060;179569059;179569058
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-85
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.1921
• 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
S/F	None	None	0.987	None	0.598	0.511	0.710634673768	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	0	0
S/P	None	None	0.999	None	0.611	0.534	0.570372710236	gnomAD-4.0.0	1.59086E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85749E-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
S/A	0.2637	likely_benign	0.2613	benign	-0.471	Destabilizing	0.973	D	0.414	neutral	None	None	None	None	N
S/C	0.6956	likely_pathogenic	0.7085	pathogenic	-0.426	Destabilizing	1.0	D	0.591	neutral	None	None	None	None	N
S/D	0.9328	likely_pathogenic	0.9353	pathogenic	-0.277	Destabilizing	0.999	D	0.538	neutral	None	None	None	None	N
S/E	0.9719	likely_pathogenic	0.9714	pathogenic	-0.262	Destabilizing	0.992	D	0.496	neutral	None	None	None	None	N
S/F	0.9002	likely_pathogenic	0.8842	pathogenic	-0.581	Destabilizing	0.987	D	0.598	neutral	None	None	None	None	N
S/G	0.4462	ambiguous	0.4806	ambiguous	-0.744	Destabilizing	0.992	D	0.421	neutral	None	None	None	None	N
S/H	0.9218	likely_pathogenic	0.9237	pathogenic	-1.252	Destabilizing	0.995	D	0.613	neutral	None	None	None	None	N
S/I	0.839	likely_pathogenic	0.8179	pathogenic	0.144	Stabilizing	0.995	D	0.629	neutral	None	None	None	None	N
S/K	0.9917	likely_pathogenic	0.9915	pathogenic	-0.738	Destabilizing	0.992	D	0.501	neutral	None	None	None	None	N
S/L	0.5568	ambiguous	0.5227	ambiguous	0.144	Stabilizing	0.983	D	0.537	neutral	None	None	None	None	N
S/M	0.8085	likely_pathogenic	0.803	pathogenic	0.217	Stabilizing	1.0	D	0.594	neutral	None	None	None	None	N
S/N	0.6965	likely_pathogenic	0.7272	pathogenic	-0.754	Destabilizing	0.997	D	0.525	neutral	None	None	None	None	N
S/P	0.9413	likely_pathogenic	0.9363	pathogenic	-0.025	Destabilizing	0.999	D	0.611	neutral	None	None	None	None	N
S/Q	0.959	likely_pathogenic	0.9604	pathogenic	-0.804	Destabilizing	0.999	D	0.597	neutral	None	None	None	None	N
S/R	0.9783	likely_pathogenic	0.9768	pathogenic	-0.693	Destabilizing	0.998	D	0.611	neutral	None	None	None	None	N
S/T	0.2522	likely_benign	0.2608	benign	-0.679	Destabilizing	0.989	D	0.428	neutral	None	None	None	None	N
S/V	0.8216	likely_pathogenic	0.808	pathogenic	-0.025	Destabilizing	0.995	D	0.564	neutral	None	None	None	None	N
S/W	0.9291	likely_pathogenic	0.9201	pathogenic	-0.657	Destabilizing	0.999	D	0.65	neutral	None	None	None	None	N
S/Y	0.8636	likely_pathogenic	0.8542	pathogenic	-0.356	Destabilizing	0.241	N	0.351	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.