TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14220	42883;42884;42885	chr2:178633841;178633840;178633839	chr2:179498568;179498567;179498566
N2AB	12579	37960;37961;37962	chr2:178633841;178633840;178633839	chr2:179498568;179498567;179498566
N2A	11652	35179;35180;35181	chr2:178633841;178633840;178633839	chr2:179498568;179498567;179498566
N2B	5155	15688;15689;15690	chr2:178633841;178633840;178633839	chr2:179498568;179498567;179498566
Novex-1	5280	16063;16064;16065	chr2:178633841;178633840;178633839	chr2:179498568;179498567;179498566
Novex-2	5347	16264;16265;16266	chr2:178633841;178633840;178633839	chr2:179498568;179498567;179498566
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-92
• Domain position: 79
• Structural Position: 169
• Q(SASA): 0.1036
• 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	rs777534842	-0.644	0.984	D	0.807	0.422	0.624477516964	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
S/F	rs777534842	-0.644	0.984	D	0.807	0.422	0.624477516964	gnomAD-4.0.0	1.36884E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.31943E-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
S/A	0.1784	likely_benign	0.1606	benign	-0.77	Destabilizing	0.64	D	0.523	neutral	N	0.434870136	None	None	N
S/C	0.1548	likely_benign	0.1575	benign	-0.351	Destabilizing	0.999	D	0.75	deleterious	N	0.445867316	None	None	N
S/D	0.8985	likely_pathogenic	0.8988	pathogenic	0.203	Stabilizing	0.919	D	0.681	prob.neutral	None	None	None	None	N
S/E	0.9463	likely_pathogenic	0.9392	pathogenic	0.223	Stabilizing	0.919	D	0.678	prob.neutral	None	None	None	None	N
S/F	0.7633	likely_pathogenic	0.7269	pathogenic	-0.846	Destabilizing	0.984	D	0.807	deleterious	D	0.574440421	None	None	N
S/G	0.2312	likely_benign	0.2571	benign	-1.047	Destabilizing	0.919	D	0.679	prob.neutral	None	None	None	None	N
S/H	0.8214	likely_pathogenic	0.8144	pathogenic	-1.391	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
S/I	0.6503	likely_pathogenic	0.5825	pathogenic	-0.135	Destabilizing	0.976	D	0.789	deleterious	None	None	None	None	N
S/K	0.9789	likely_pathogenic	0.9757	pathogenic	-0.463	Destabilizing	0.919	D	0.679	prob.neutral	None	None	None	None	N
S/L	0.4184	ambiguous	0.3717	ambiguous	-0.135	Destabilizing	0.851	D	0.766	deleterious	None	None	None	None	N
S/M	0.5052	ambiguous	0.5255	ambiguous	0.05	Stabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
S/N	0.5912	likely_pathogenic	0.5627	ambiguous	-0.406	Destabilizing	0.919	D	0.671	neutral	None	None	None	None	N
S/P	0.9701	likely_pathogenic	0.9749	pathogenic	-0.312	Destabilizing	0.984	D	0.773	deleterious	D	0.535538861	None	None	N
S/Q	0.9074	likely_pathogenic	0.9006	pathogenic	-0.481	Destabilizing	0.988	D	0.755	deleterious	None	None	None	None	N
S/R	0.9646	likely_pathogenic	0.9569	pathogenic	-0.447	Destabilizing	0.976	D	0.767	deleterious	None	None	None	None	N
S/T	0.0729	likely_benign	0.0882	benign	-0.477	Destabilizing	0.016	N	0.277	neutral	N	0.436612201	None	None	N
S/V	0.4994	ambiguous	0.4511	ambiguous	-0.312	Destabilizing	0.851	D	0.765	deleterious	None	None	None	None	N
S/W	0.8827	likely_pathogenic	0.8746	pathogenic	-0.81	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
S/Y	0.718	likely_pathogenic	0.6835	pathogenic	-0.541	Destabilizing	0.995	D	0.792	deleterious	N	0.491751066	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.