TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28571	85936;85937;85938	chr2:178560421;178560420;178560419	chr2:179425148;179425147;179425146
N2AB	26930	81013;81014;81015	chr2:178560421;178560420;178560419	chr2:179425148;179425147;179425146
N2A	26003	78232;78233;78234	chr2:178560421;178560420;178560419	chr2:179425148;179425147;179425146
N2B	19506	58741;58742;58743	chr2:178560421;178560420;178560419	chr2:179425148;179425147;179425146
Novex-1	19631	59116;59117;59118	chr2:178560421;178560420;178560419	chr2:179425148;179425147;179425146
Novex-2	19698	59317;59318;59319	chr2:178560421;178560420;178560419	chr2:179425148;179425147;179425146
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Fn3-96
• Domain position: 22
• Structural Position: 24
• Q(SASA): 0.0929
• 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
W/R	None	None	0.982	D	0.88	0.83	0.8918447195	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	3.66327E-05
W/S	None	None	0.322	D	0.74	0.617	0.871759669856	gnomAD-4.0.0	6.84259E-07	None	None	None	None	N	None	0	0	None	0	2.52283E-05	None	0	0	0	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
W/A	0.992	likely_pathogenic	0.9871	pathogenic	-3.312	Highly Destabilizing	0.91	D	0.856	deleterious	None	None	None	None	N
W/C	0.9931	likely_pathogenic	0.9892	pathogenic	-1.917	Destabilizing	0.999	D	0.847	deleterious	D	0.683590493	None	None	N
W/D	0.9994	likely_pathogenic	0.9988	pathogenic	-3.867	Highly Destabilizing	0.986	D	0.88	deleterious	None	None	None	None	N
W/E	0.9994	likely_pathogenic	0.9987	pathogenic	-3.74	Highly Destabilizing	0.986	D	0.878	deleterious	None	None	None	None	N
W/F	0.5626	ambiguous	0.5415	ambiguous	-2.203	Highly Destabilizing	0.993	D	0.799	deleterious	None	None	None	None	N
W/G	0.9713	likely_pathogenic	0.9455	pathogenic	-3.565	Highly Destabilizing	0.885	D	0.831	deleterious	D	0.683590493	None	None	N
W/H	0.9927	likely_pathogenic	0.9894	pathogenic	-2.889	Highly Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
W/I	0.9799	likely_pathogenic	0.9726	pathogenic	-2.333	Highly Destabilizing	0.993	D	0.883	deleterious	None	None	None	None	N
W/K	0.9995	likely_pathogenic	0.999	pathogenic	-2.927	Highly Destabilizing	0.986	D	0.877	deleterious	None	None	None	None	N
W/L	0.9487	likely_pathogenic	0.931	pathogenic	-2.333	Highly Destabilizing	0.939	D	0.841	deleterious	D	0.65010878	None	None	N
W/M	0.9921	likely_pathogenic	0.9894	pathogenic	-1.791	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
W/N	0.9992	likely_pathogenic	0.9985	pathogenic	-3.701	Highly Destabilizing	0.986	D	0.884	deleterious	None	None	None	None	N
W/P	0.9985	likely_pathogenic	0.997	pathogenic	-2.692	Highly Destabilizing	0.993	D	0.885	deleterious	None	None	None	None	N
W/Q	0.9992	likely_pathogenic	0.9984	pathogenic	-3.468	Highly Destabilizing	0.993	D	0.859	deleterious	None	None	None	None	N
W/R	0.9978	likely_pathogenic	0.9957	pathogenic	-2.761	Highly Destabilizing	0.982	D	0.88	deleterious	D	0.683590493	None	None	N
W/S	0.9878	likely_pathogenic	0.978	pathogenic	-3.759	Highly Destabilizing	0.322	N	0.74	deleterious	D	0.683590493	None	None	N
W/T	0.9943	likely_pathogenic	0.9905	pathogenic	-3.55	Highly Destabilizing	0.973	D	0.832	deleterious	None	None	None	None	N
W/V	0.9794	likely_pathogenic	0.9727	pathogenic	-2.692	Highly Destabilizing	0.986	D	0.876	deleterious	None	None	None	None	N
W/Y	0.899	likely_pathogenic	0.8841	pathogenic	-2.109	Highly Destabilizing	0.998	D	0.794	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.