TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8530	25813;25814;25815	chr2:178717146;178717145;178717144	chr2:179581873;179581872;179581871
N2AB	8213	24862;24863;24864	chr2:178717146;178717145;178717144	chr2:179581873;179581872;179581871
N2A	7286	22081;22082;22083	chr2:178717146;178717145;178717144	chr2:179581873;179581872;179581871
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-70
• Domain position: 75
• Structural Position: 158
• Q(SASA): 0.0613
• 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
A/E	rs2077607600	None	1.0	D	0.832	0.662	0.794151654302	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
A/E	rs2077607600	None	1.0	D	0.832	0.662	0.794151654302	gnomAD-4.0.0	6.57142E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47016E-05	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
A/C	0.9007	likely_pathogenic	0.9017	pathogenic	-1.16	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
A/D	0.9981	likely_pathogenic	0.9979	pathogenic	-1.923	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
A/E	0.9967	likely_pathogenic	0.996	pathogenic	-1.756	Destabilizing	1.0	D	0.832	deleterious	D	0.65737199	None	None	N
A/F	0.9634	likely_pathogenic	0.96	pathogenic	-0.687	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
A/G	0.3792	ambiguous	0.4082	ambiguous	-1.546	Destabilizing	0.998	D	0.615	neutral	D	0.609112102	None	None	N
A/H	0.9973	likely_pathogenic	0.997	pathogenic	-1.86	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
A/I	0.7014	likely_pathogenic	0.6457	pathogenic	0.084	Stabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
A/K	0.999	likely_pathogenic	0.9988	pathogenic	-1.11	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
A/L	0.7467	likely_pathogenic	0.6908	pathogenic	0.084	Stabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
A/M	0.9017	likely_pathogenic	0.8786	pathogenic	-0.225	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
A/N	0.9944	likely_pathogenic	0.9933	pathogenic	-1.283	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
A/P	0.9906	likely_pathogenic	0.9918	pathogenic	-0.267	Destabilizing	1.0	D	0.869	deleterious	D	0.65737199	None	None	N
A/Q	0.992	likely_pathogenic	0.9908	pathogenic	-1.135	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
A/R	0.9942	likely_pathogenic	0.9937	pathogenic	-1.195	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
A/S	0.4639	ambiguous	0.4445	ambiguous	-1.747	Destabilizing	0.992	D	0.623	neutral	D	0.611928439	None	None	N
A/T	0.6156	likely_pathogenic	0.5711	pathogenic	-1.455	Destabilizing	0.998	D	0.689	prob.neutral	D	0.640747216	None	None	N
A/V	0.394	ambiguous	0.3504	ambiguous	-0.267	Destabilizing	0.989	D	0.399	neutral	N	0.507126217	None	None	N
A/W	0.9989	likely_pathogenic	0.9989	pathogenic	-1.35	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
A/Y	0.9934	likely_pathogenic	0.9931	pathogenic	-0.825	Destabilizing	1.0	D	0.881	deleterious	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.