TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18081	54466;54467;54468	chr2:178604848;178604847;178604846	chr2:179469575;179469574;179469573
N2AB	16440	49543;49544;49545	chr2:178604848;178604847;178604846	chr2:179469575;179469574;179469573
N2A	15513	46762;46763;46764	chr2:178604848;178604847;178604846	chr2:179469575;179469574;179469573
N2B	9016	27271;27272;27273	chr2:178604848;178604847;178604846	chr2:179469575;179469574;179469573
Novex-1	9141	27646;27647;27648	chr2:178604848;178604847;178604846	chr2:179469575;179469574;179469573
Novex-2	9208	27847;27848;27849	chr2:178604848;178604847;178604846	chr2:179469575;179469574;179469573
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-19
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.1579
• 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	None	None	1.0	N	0.825	0.497	0.689175263246	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-06	0	0
S/T	None	None	0.999	N	0.485	0.369	0.379707525713	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	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
S/A	0.2634	likely_benign	0.2391	benign	-0.814	Destabilizing	0.997	D	0.455	neutral	N	0.47729163	None	None	N
S/C	0.3224	likely_benign	0.2879	benign	-0.467	Destabilizing	1.0	D	0.745	deleterious	N	0.496765465	None	None	N
S/D	0.953	likely_pathogenic	0.9353	pathogenic	-1.244	Destabilizing	0.999	D	0.604	neutral	None	None	None	None	N
S/E	0.9542	likely_pathogenic	0.9452	pathogenic	-1.071	Destabilizing	0.999	D	0.591	neutral	None	None	None	None	N
S/F	0.7412	likely_pathogenic	0.6616	pathogenic	-0.53	Destabilizing	1.0	D	0.825	deleterious	N	0.491739035	None	None	N
S/G	0.3723	ambiguous	0.3175	benign	-1.193	Destabilizing	0.999	D	0.487	neutral	None	None	None	None	N
S/H	0.785	likely_pathogenic	0.7319	pathogenic	-1.509	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
S/I	0.8121	likely_pathogenic	0.7679	pathogenic	0.146	Stabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
S/K	0.98	likely_pathogenic	0.9717	pathogenic	-0.374	Destabilizing	0.999	D	0.589	neutral	None	None	None	None	N
S/L	0.6421	likely_pathogenic	0.5696	pathogenic	0.146	Stabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
S/M	0.6083	likely_pathogenic	0.5605	ambiguous	0.074	Stabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
S/N	0.5887	likely_pathogenic	0.5134	ambiguous	-0.92	Destabilizing	0.999	D	0.586	neutral	None	None	None	None	N
S/P	0.9978	likely_pathogenic	0.9968	pathogenic	-0.14	Destabilizing	1.0	D	0.815	deleterious	D	0.532555901	None	None	N
S/Q	0.8909	likely_pathogenic	0.8753	pathogenic	-0.699	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
S/R	0.9679	likely_pathogenic	0.9546	pathogenic	-0.713	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
S/T	0.288	likely_benign	0.2636	benign	-0.627	Destabilizing	0.999	D	0.485	neutral	N	0.509904965	None	None	N
S/V	0.7408	likely_pathogenic	0.7065	pathogenic	-0.14	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
S/W	0.8183	likely_pathogenic	0.7607	pathogenic	-0.794	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
S/Y	0.5815	likely_pathogenic	0.5006	ambiguous	-0.376	Destabilizing	1.0	D	0.826	deleterious	N	0.493687592	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.