TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19375	58348;58349;58350	chr2:178594371;178594370;178594369	chr2:179459098;179459097;179459096
N2AB	17734	53425;53426;53427	chr2:178594371;178594370;178594369	chr2:179459098;179459097;179459096
N2A	16807	50644;50645;50646	chr2:178594371;178594370;178594369	chr2:179459098;179459097;179459096
N2B	10310	31153;31154;31155	chr2:178594371;178594370;178594369	chr2:179459098;179459097;179459096
Novex-1	10435	31528;31529;31530	chr2:178594371;178594370;178594369	chr2:179459098;179459097;179459096
Novex-2	10502	31729;31730;31731	chr2:178594371;178594370;178594369	chr2:179459098;179459097;179459096
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: Fn3-28
• Domain position: 92
• Structural Position: 125
• Q(SASA): 0.5076
• 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/R	rs374594411	0.113	0.997	N	0.675	0.205	None	gnomAD-2.1.1	2.61E-05	None	None	None	None	N	None	8.33E-05	0	None	0	0	None	0	None	0	4.03E-05	0
K/R	rs374594411	0.113	0.997	N	0.675	0.205	None	gnomAD-3.1.2	3.95E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	8.83E-05	0	0
K/R	rs374594411	0.113	0.997	N	0.675	0.205	None	gnomAD-4.0.0	1.75368E-05	None	None	None	None	N	None	2.6992E-05	0	None	0	0	None	0	1.66389E-04	2.04808E-05	0	1.61996E-05

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	0.6969	likely_pathogenic	0.6794	pathogenic	0.042	Stabilizing	0.998	D	0.783	deleterious	None	None	None	None	N
K/C	0.9331	likely_pathogenic	0.926	pathogenic	-0.399	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
K/D	0.8614	likely_pathogenic	0.8636	pathogenic	-0.297	Destabilizing	0.999	D	0.833	deleterious	None	None	None	None	N
K/E	0.5798	likely_pathogenic	0.5666	pathogenic	-0.298	Destabilizing	0.997	D	0.705	prob.delet.	N	0.43570549	None	None	N
K/F	0.9573	likely_pathogenic	0.948	pathogenic	-0.251	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
K/G	0.7516	likely_pathogenic	0.7433	pathogenic	-0.106	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
K/H	0.6765	likely_pathogenic	0.6575	pathogenic	-0.208	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
K/I	0.7422	likely_pathogenic	0.7173	pathogenic	0.353	Stabilizing	0.999	D	0.824	deleterious	N	0.477958015	None	None	N
K/L	0.6749	likely_pathogenic	0.6522	pathogenic	0.353	Stabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
K/M	0.6172	likely_pathogenic	0.5895	pathogenic	-0.096	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
K/N	0.7977	likely_pathogenic	0.787	pathogenic	0.023	Stabilizing	0.999	D	0.785	deleterious	N	0.496657948	None	None	N
K/P	0.712	likely_pathogenic	0.6826	pathogenic	0.274	Stabilizing	0.999	D	0.833	deleterious	None	None	None	None	N
K/Q	0.3619	ambiguous	0.3484	ambiguous	-0.096	Destabilizing	0.999	D	0.77	deleterious	N	0.488019822	None	None	N
K/R	0.1412	likely_benign	0.1352	benign	-0.081	Destabilizing	0.997	D	0.675	prob.neutral	N	0.510568608	None	None	N
K/S	0.7662	likely_pathogenic	0.7549	pathogenic	-0.315	Destabilizing	0.998	D	0.724	deleterious	None	None	None	None	N
K/T	0.5229	ambiguous	0.5005	ambiguous	-0.193	Destabilizing	0.999	D	0.825	deleterious	N	0.508835024	None	None	N
K/V	0.6726	likely_pathogenic	0.6478	pathogenic	0.274	Stabilizing	0.999	D	0.832	deleterious	None	None	None	None	N
K/W	0.9656	likely_pathogenic	0.9553	pathogenic	-0.369	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
K/Y	0.9024	likely_pathogenic	0.8857	pathogenic	-0.015	Destabilizing	1.0	D	0.837	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.