TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23243	69952;69953;69954	chr2:178576405;178576404;178576403	chr2:179441132;179441131;179441130
N2AB	21602	65029;65030;65031	chr2:178576405;178576404;178576403	chr2:179441132;179441131;179441130
N2A	20675	62248;62249;62250	chr2:178576405;178576404;178576403	chr2:179441132;179441131;179441130
N2B	14178	42757;42758;42759	chr2:178576405;178576404;178576403	chr2:179441132;179441131;179441130
Novex-1	14303	43132;43133;43134	chr2:178576405;178576404;178576403	chr2:179441132;179441131;179441130
Novex-2	14370	43333;43334;43335	chr2:178576405;178576404;178576403	chr2:179441132;179441131;179441130
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-57
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.3436
• Predicted PPI site: I

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
P/S	rs1221599663	-1.267	1.0	N	0.855	0.434	0.34854441366	gnomAD-2.1.1	4.71E-06	None	None	None	None	I	None	0	0	None	0	0	None	4.24E-05	None	0	0	0
P/S	rs1221599663	-1.267	1.0	N	0.855	0.434	0.34854441366	gnomAD-4.0.0	3.39479E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.95069E-05	0	0	1.60318E-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
P/A	0.1538	likely_benign	0.1208	benign	-1.433	Destabilizing	1.0	D	0.837	deleterious	N	0.460196154	None	None	I
P/C	0.7488	likely_pathogenic	0.6371	pathogenic	-0.922	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	I
P/D	0.9559	likely_pathogenic	0.9117	pathogenic	-1.71	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
P/E	0.7722	likely_pathogenic	0.6566	pathogenic	-1.754	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	I
P/F	0.8086	likely_pathogenic	0.7191	pathogenic	-1.332	Destabilizing	1.0	D	0.918	deleterious	None	None	None	None	I
P/G	0.7292	likely_pathogenic	0.6434	pathogenic	-1.701	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	I
P/H	0.5871	likely_pathogenic	0.4697	ambiguous	-1.289	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	I
P/I	0.6435	likely_pathogenic	0.5281	ambiguous	-0.802	Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	I
P/K	0.6367	likely_pathogenic	0.5082	ambiguous	-1.097	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	I
P/L	0.3677	ambiguous	0.2835	benign	-0.802	Destabilizing	1.0	D	0.901	deleterious	N	0.505214346	None	None	I
P/M	0.5972	likely_pathogenic	0.5001	ambiguous	-0.514	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	I
P/N	0.8592	likely_pathogenic	0.7754	pathogenic	-0.846	Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	I
P/Q	0.4474	ambiguous	0.3468	ambiguous	-1.124	Destabilizing	1.0	D	0.871	deleterious	N	0.500477405	None	None	I
P/R	0.5075	ambiguous	0.3864	ambiguous	-0.539	Destabilizing	1.0	D	0.911	deleterious	N	0.503946898	None	None	I
P/S	0.3919	ambiguous	0.296	benign	-1.262	Destabilizing	1.0	D	0.855	deleterious	N	0.490184283	None	None	I
P/T	0.4457	ambiguous	0.3386	benign	-1.213	Destabilizing	1.0	D	0.853	deleterious	N	0.501744852	None	None	I
P/V	0.5226	ambiguous	0.4121	ambiguous	-0.979	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	I
P/W	0.9431	likely_pathogenic	0.9008	pathogenic	-1.487	Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	I
P/Y	0.8394	likely_pathogenic	0.7515	pathogenic	-1.202	Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	I

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.