TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35296	106111;106112;106113	chr2:178530729;178530728;178530727	chr2:179395456;179395455;179395454
N2AB	33655	101188;101189;101190	chr2:178530729;178530728;178530727	chr2:179395456;179395455;179395454
N2A	32728	98407;98408;98409	chr2:178530729;178530728;178530727	chr2:179395456;179395455;179395454
N2B	26231	78916;78917;78918	chr2:178530729;178530728;178530727	chr2:179395456;179395455;179395454
Novex-1	26356	79291;79292;79293	chr2:178530729;178530728;178530727	chr2:179395456;179395455;179395454
Novex-2	26423	79492;79493;79494	chr2:178530729;178530728;178530727	chr2:179395456;179395455;179395454
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-165
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.5771
• 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/V	None	None	0.626	N	0.422	0.218	0.12205267543	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
A/C	0.6584	likely_pathogenic	0.6904	pathogenic	-0.709	Destabilizing	0.997	D	0.456	neutral	None	None	None	None	N
A/D	0.5394	ambiguous	0.4901	ambiguous	-0.553	Destabilizing	0.922	D	0.487	neutral	N	0.474609729	None	None	N
A/E	0.4927	ambiguous	0.4465	ambiguous	-0.719	Destabilizing	0.816	D	0.41	neutral	None	None	None	None	N
A/F	0.41	ambiguous	0.4071	ambiguous	-0.929	Destabilizing	0.969	D	0.606	neutral	None	None	None	None	N
A/G	0.1952	likely_benign	0.1972	benign	-0.236	Destabilizing	0.409	N	0.457	neutral	N	0.499468101	None	None	N
A/H	0.7346	likely_pathogenic	0.7284	pathogenic	-0.326	Destabilizing	0.997	D	0.612	neutral	None	None	None	None	N
A/I	0.3023	likely_benign	0.3058	benign	-0.35	Destabilizing	0.94	D	0.443	neutral	None	None	None	None	N
A/K	0.7254	likely_pathogenic	0.7077	pathogenic	-0.579	Destabilizing	0.816	D	0.401	neutral	None	None	None	None	N
A/L	0.3129	likely_benign	0.3014	benign	-0.35	Destabilizing	0.69	D	0.41	neutral	None	None	None	None	N
A/M	0.3706	ambiguous	0.3709	ambiguous	-0.372	Destabilizing	0.997	D	0.499	neutral	None	None	None	None	N
A/N	0.4634	ambiguous	0.4344	ambiguous	-0.23	Destabilizing	0.94	D	0.501	neutral	None	None	None	None	N
A/P	0.5481	ambiguous	0.4108	ambiguous	-0.274	Destabilizing	0.96	D	0.478	neutral	N	0.454754531	None	None	N
A/Q	0.6227	likely_pathogenic	0.6114	pathogenic	-0.536	Destabilizing	0.969	D	0.479	neutral	None	None	None	None	N
A/R	0.6604	likely_pathogenic	0.6437	pathogenic	-0.11	Destabilizing	0.94	D	0.483	neutral	None	None	None	None	N
A/S	0.1436	likely_benign	0.144	benign	-0.388	Destabilizing	0.019	N	0.213	neutral	N	0.470355915	None	None	N
A/T	0.1286	likely_benign	0.1328	benign	-0.483	Destabilizing	0.043	N	0.284	neutral	N	0.413809199	None	None	N
A/V	0.1675	likely_benign	0.1708	benign	-0.274	Destabilizing	0.626	D	0.422	neutral	N	0.414675991	None	None	N
A/W	0.8559	likely_pathogenic	0.8479	pathogenic	-1.057	Destabilizing	0.997	D	0.679	prob.neutral	None	None	None	None	N
A/Y	0.5964	likely_pathogenic	0.5885	pathogenic	-0.71	Destabilizing	0.99	D	0.608	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.