TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6916	20971;20972;20973	chr2:178725458;178725457;178725456	chr2:179590185;179590184;179590183
N2AB	6599	20020;20021;20022	chr2:178725458;178725457;178725456	chr2:179590185;179590184;179590183
N2A	5672	17239;17240;17241	chr2:178725458;178725457;178725456	chr2:179590185;179590184;179590183
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-53
• Domain position: 63
• Structural Position: 143
• Q(SASA): 0.7555
• 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
K/N	None	None	0.642	N	0.343	0.1	0.149567049428	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25001E-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
K/A	0.1704	likely_benign	0.1596	benign	-0.1	Destabilizing	0.329	N	0.369	neutral	None	None	None	None	N
K/C	0.5934	likely_pathogenic	0.5602	ambiguous	-0.025	Destabilizing	0.995	D	0.335	neutral	None	None	None	None	N
K/D	0.2635	likely_benign	0.272	benign	-0.048	Destabilizing	0.704	D	0.373	neutral	None	None	None	None	N
K/E	0.0938	likely_benign	0.0942	benign	-0.025	Destabilizing	0.27	N	0.321	neutral	N	0.447588991	None	None	N
K/F	0.5362	ambiguous	0.5322	ambiguous	-0.176	Destabilizing	0.017	N	0.321	neutral	None	None	None	None	N
K/G	0.2377	likely_benign	0.2313	benign	-0.366	Destabilizing	0.704	D	0.382	neutral	None	None	None	None	N
K/H	0.21	likely_benign	0.2008	benign	-0.788	Destabilizing	0.944	D	0.337	neutral	None	None	None	None	N
K/I	0.2407	likely_benign	0.2331	benign	0.539	Stabilizing	0.023	N	0.315	neutral	N	0.46924092	None	None	N
K/L	0.2488	likely_benign	0.2353	benign	0.539	Stabilizing	0.329	N	0.383	neutral	None	None	None	None	N
K/M	0.1653	likely_benign	0.1594	benign	0.553	Stabilizing	0.944	D	0.333	neutral	None	None	None	None	N
K/N	0.1784	likely_benign	0.1805	benign	0.213	Stabilizing	0.642	D	0.343	neutral	N	0.422919833	None	None	N
K/P	0.6161	likely_pathogenic	0.5942	pathogenic	0.356	Stabilizing	0.944	D	0.379	neutral	None	None	None	None	N
K/Q	0.1065	likely_benign	0.1008	benign	-0.017	Destabilizing	0.023	N	0.285	neutral	N	0.473948873	None	None	N
K/R	0.0773	likely_benign	0.0744	benign	-0.111	Destabilizing	0.006	N	0.283	neutral	N	0.416767438	None	None	N
K/S	0.1866	likely_benign	0.18	benign	-0.321	Destabilizing	0.085	N	0.248	neutral	None	None	None	None	N
K/T	0.1063	likely_benign	0.1018	benign	-0.136	Destabilizing	0.473	N	0.357	neutral	N	0.504021063	None	None	N
K/V	0.2098	likely_benign	0.1918	benign	0.356	Stabilizing	0.329	N	0.366	neutral	None	None	None	None	N
K/W	0.6248	likely_pathogenic	0.6255	pathogenic	-0.12	Destabilizing	0.995	D	0.344	neutral	None	None	None	None	N
K/Y	0.4231	ambiguous	0.416	ambiguous	0.215	Stabilizing	0.807	D	0.389	neutral	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.