TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19568	58927;58928;58929	chr2:178593598;178593597;178593596	chr2:179458325;179458324;179458323
N2AB	17927	54004;54005;54006	chr2:178593598;178593597;178593596	chr2:179458325;179458324;179458323
N2A	17000	51223;51224;51225	chr2:178593598;178593597;178593596	chr2:179458325;179458324;179458323
N2B	10503	31732;31733;31734	chr2:178593598;178593597;178593596	chr2:179458325;179458324;179458323
Novex-1	10628	32107;32108;32109	chr2:178593598;178593597;178593596	chr2:179458325;179458324;179458323
Novex-2	10695	32308;32309;32310	chr2:178593598;178593597;178593596	chr2:179458325;179458324;179458323
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: Fn3-29
• Domain position: 90
• Structural Position: 123
• Q(SASA): 0.207
• 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/C	rs1465396608	-0.323	1.0	N	0.797	0.486	0.535439087667	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
S/C	rs1465396608	-0.323	1.0	N	0.797	0.486	0.535439087667	gnomAD-4.0.0	1.59417E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43678E-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
S/A	0.3805	ambiguous	0.3149	benign	-0.432	Destabilizing	0.994	D	0.671	prob.neutral	N	0.516508437	None	None	N
S/C	0.5052	ambiguous	0.4398	ambiguous	-0.101	Destabilizing	1.0	D	0.797	deleterious	N	0.510531761	None	None	N
S/D	0.9834	likely_pathogenic	0.9824	pathogenic	0.251	Stabilizing	0.998	D	0.774	deleterious	None	None	None	None	N
S/E	0.9924	likely_pathogenic	0.9925	pathogenic	0.383	Stabilizing	0.998	D	0.787	deleterious	None	None	None	None	N
S/F	0.9837	likely_pathogenic	0.9799	pathogenic	-0.524	Destabilizing	0.999	D	0.827	deleterious	N	0.503441417	None	None	N
S/G	0.3917	ambiguous	0.3534	ambiguous	-0.773	Destabilizing	0.998	D	0.745	deleterious	None	None	None	None	N
S/H	0.9843	likely_pathogenic	0.9842	pathogenic	-1.005	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
S/I	0.9641	likely_pathogenic	0.9551	pathogenic	0.402	Stabilizing	0.999	D	0.821	deleterious	None	None	None	None	N
S/K	0.9986	likely_pathogenic	0.9986	pathogenic	0.36	Stabilizing	0.998	D	0.775	deleterious	None	None	None	None	N
S/L	0.844	likely_pathogenic	0.8054	pathogenic	0.402	Stabilizing	0.999	D	0.79	deleterious	None	None	None	None	N
S/M	0.8894	likely_pathogenic	0.8667	pathogenic	0.209	Stabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
S/N	0.9494	likely_pathogenic	0.9482	pathogenic	-0.084	Destabilizing	0.998	D	0.801	deleterious	None	None	None	None	N
S/P	0.987	likely_pathogenic	0.9844	pathogenic	0.159	Stabilizing	0.999	D	0.843	deleterious	N	0.492498214	None	None	N
S/Q	0.9914	likely_pathogenic	0.9912	pathogenic	0.088	Stabilizing	0.999	D	0.852	deleterious	None	None	None	None	N
S/R	0.9975	likely_pathogenic	0.9974	pathogenic	0.037	Stabilizing	0.999	D	0.845	deleterious	None	None	None	None	N
S/T	0.2442	likely_benign	0.2295	benign	0.009	Stabilizing	0.997	D	0.751	deleterious	N	0.468850563	None	None	N
S/V	0.9207	likely_pathogenic	0.9024	pathogenic	0.159	Stabilizing	0.999	D	0.819	deleterious	None	None	None	None	N
S/W	0.9865	likely_pathogenic	0.9846	pathogenic	-0.642	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
S/Y	0.9813	likely_pathogenic	0.9786	pathogenic	-0.189	Destabilizing	0.999	D	0.857	deleterious	N	0.521545672	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.