TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22192	66799;66800;66801	chr2:178581694;178581693;178581692	chr2:179446421;179446420;179446419
N2AB	20551	61876;61877;61878	chr2:178581694;178581693;178581692	chr2:179446421;179446420;179446419
N2A	19624	59095;59096;59097	chr2:178581694;178581693;178581692	chr2:179446421;179446420;179446419
N2B	13127	39604;39605;39606	chr2:178581694;178581693;178581692	chr2:179446421;179446420;179446419
Novex-1	13252	39979;39980;39981	chr2:178581694;178581693;178581692	chr2:179446421;179446420;179446419
Novex-2	13319	40180;40181;40182	chr2:178581694;178581693;178581692	chr2:179446421;179446420;179446419
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Fn3-49
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.1064
• 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
L/F	None	None	0.988	N	0.763	0.286	0.581410409299	gnomAD-4.0.0	1.59535E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86425E-06	0	0
L/P	None	None	0.998	N	0.816	0.572	0.838659699283	gnomAD-4.0.0	2.40066E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	1.31251E-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
L/A	0.6053	likely_pathogenic	0.6388	pathogenic	-3.086	Highly Destabilizing	0.938	D	0.645	neutral	None	None	None	None	N
L/C	0.6837	likely_pathogenic	0.7074	pathogenic	-2.266	Highly Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
L/D	0.9723	likely_pathogenic	0.9763	pathogenic	-3.632	Highly Destabilizing	0.998	D	0.817	deleterious	None	None	None	None	N
L/E	0.8287	likely_pathogenic	0.8492	pathogenic	-3.362	Highly Destabilizing	0.995	D	0.793	deleterious	None	None	None	None	N
L/F	0.3584	ambiguous	0.3492	ambiguous	-1.806	Destabilizing	0.988	D	0.763	deleterious	N	0.485734452	None	None	N
L/G	0.9246	likely_pathogenic	0.9396	pathogenic	-3.643	Highly Destabilizing	0.995	D	0.763	deleterious	None	None	None	None	N
L/H	0.6134	likely_pathogenic	0.6483	pathogenic	-3.1	Highly Destabilizing	0.999	D	0.803	deleterious	N	0.511592902	None	None	N
L/I	0.1226	likely_benign	0.1198	benign	-1.426	Destabilizing	0.825	D	0.604	neutral	N	0.384282166	None	None	N
L/K	0.7415	likely_pathogenic	0.7814	pathogenic	-2.491	Highly Destabilizing	0.995	D	0.748	deleterious	None	None	None	None	N
L/M	0.1684	likely_benign	0.175	benign	-1.462	Destabilizing	0.995	D	0.769	deleterious	None	None	None	None	N
L/N	0.8662	likely_pathogenic	0.865	pathogenic	-2.987	Highly Destabilizing	0.998	D	0.813	deleterious	None	None	None	None	N
L/P	0.9933	likely_pathogenic	0.995	pathogenic	-1.968	Destabilizing	0.998	D	0.816	deleterious	N	0.500602309	None	None	N
L/Q	0.5139	ambiguous	0.5641	pathogenic	-2.765	Highly Destabilizing	0.998	D	0.792	deleterious	None	None	None	None	N
L/R	0.6303	likely_pathogenic	0.6902	pathogenic	-2.217	Highly Destabilizing	0.994	D	0.796	deleterious	N	0.488694612	None	None	N
L/S	0.773	likely_pathogenic	0.8044	pathogenic	-3.604	Highly Destabilizing	0.995	D	0.751	deleterious	None	None	None	None	N
L/T	0.537	ambiguous	0.5831	pathogenic	-3.196	Highly Destabilizing	0.991	D	0.741	deleterious	None	None	None	None	N
L/V	0.1324	likely_benign	0.1326	benign	-1.968	Destabilizing	0.067	N	0.349	neutral	N	0.415719793	None	None	N
L/W	0.6413	likely_pathogenic	0.6825	pathogenic	-2.236	Highly Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
L/Y	0.6781	likely_pathogenic	0.6803	pathogenic	-2.048	Highly Destabilizing	0.995	D	0.782	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.