TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18586	55981;55982;55983	chr2:178601148;178601147;178601146	chr2:179465875;179465874;179465873
N2AB	16945	51058;51059;51060	chr2:178601148;178601147;178601146	chr2:179465875;179465874;179465873
N2A	16018	48277;48278;48279	chr2:178601148;178601147;178601146	chr2:179465875;179465874;179465873
N2B	9521	28786;28787;28788	chr2:178601148;178601147;178601146	chr2:179465875;179465874;179465873
Novex-1	9646	29161;29162;29163	chr2:178601148;178601147;178601146	chr2:179465875;179465874;179465873
Novex-2	9713	29362;29363;29364	chr2:178601148;178601147;178601146	chr2:179465875;179465874;179465873
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: Fn3-23
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.1545
• 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	rs773983711	-1.595	0.999	N	0.844	0.319	0.58308304948	gnomAD-2.1.1	5.25E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.08E-05	0
L/F	rs773983711	-1.595	0.999	N	0.844	0.319	0.58308304948	gnomAD-4.0.0	7.18266E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.24618E-07	0	0
L/I	None	None	0.962	N	0.688	0.192	0.432379865206	gnomAD-4.0.0	1.43653E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.84924E-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	0.9308	likely_pathogenic	0.8571	pathogenic	-2.489	Highly Destabilizing	0.994	D	0.684	prob.neutral	None	None	None	None	N
L/C	0.887	likely_pathogenic	0.8247	pathogenic	-1.921	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
L/D	0.9985	likely_pathogenic	0.9969	pathogenic	-2.861	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
L/E	0.9911	likely_pathogenic	0.9818	pathogenic	-2.663	Highly Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
L/F	0.8105	likely_pathogenic	0.7698	pathogenic	-1.446	Destabilizing	0.999	D	0.844	deleterious	N	0.486512023	None	None	N
L/G	0.9803	likely_pathogenic	0.9616	pathogenic	-3.006	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
L/H	0.9884	likely_pathogenic	0.9791	pathogenic	-2.463	Highly Destabilizing	1.0	D	0.856	deleterious	D	0.52639429	None	None	N
L/I	0.236	likely_benign	0.1698	benign	-1.006	Destabilizing	0.962	D	0.688	prob.neutral	N	0.515796361	None	None	N
L/K	0.9869	likely_pathogenic	0.9806	pathogenic	-1.855	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
L/M	0.3479	ambiguous	0.2918	benign	-1.103	Destabilizing	0.999	D	0.802	deleterious	None	None	None	None	N
L/N	0.9853	likely_pathogenic	0.969	pathogenic	-2.131	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
L/P	0.9115	likely_pathogenic	0.8294	pathogenic	-1.481	Destabilizing	1.0	D	0.869	deleterious	N	0.433988628	None	None	N
L/Q	0.9722	likely_pathogenic	0.9473	pathogenic	-2.039	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
L/R	0.9804	likely_pathogenic	0.9702	pathogenic	-1.561	Destabilizing	1.0	D	0.853	deleterious	D	0.52639429	None	None	N
L/S	0.9893	likely_pathogenic	0.9699	pathogenic	-2.803	Highly Destabilizing	0.999	D	0.819	deleterious	None	None	None	None	N
L/T	0.9118	likely_pathogenic	0.8106	pathogenic	-2.467	Highly Destabilizing	0.998	D	0.789	deleterious	None	None	None	None	N
L/V	0.1855	likely_benign	0.1207	benign	-1.481	Destabilizing	0.619	D	0.327	neutral	N	0.438890228	None	None	N
L/W	0.9778	likely_pathogenic	0.966	pathogenic	-1.819	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
L/Y	0.9777	likely_pathogenic	0.9679	pathogenic	-1.546	Destabilizing	1.0	D	0.811	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.