TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22410	67453;67454;67455	chr2:178580059;178580058;178580057	chr2:179444786;179444785;179444784
N2AB	20769	62530;62531;62532	chr2:178580059;178580058;178580057	chr2:179444786;179444785;179444784
N2A	19842	59749;59750;59751	chr2:178580059;178580058;178580057	chr2:179444786;179444785;179444784
N2B	13345	40258;40259;40260	chr2:178580059;178580058;178580057	chr2:179444786;179444785;179444784
Novex-1	13470	40633;40634;40635	chr2:178580059;178580058;178580057	chr2:179444786;179444785;179444784
Novex-2	13537	40834;40835;40836	chr2:178580059;178580058;178580057	chr2:179444786;179444785;179444784
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: Fn3-50
• Domain position: 57
• Structural Position: 88
• Q(SASA): 0.3777
• 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/Q	rs773410270	-0.054	0.983	N	0.609	0.348	0.237489013734	gnomAD-4.0.0	3.1843E-06	None	None	None	None	N	None	0	0	None	0	5.55031E-05	None	0	0	0	0	0
K/T	rs1559493839	None	0.967	N	0.61	0.369	0.373897652646	gnomAD-4.0.0	1.59215E-06	None	None	None	None	N	None	0	2.28707E-05	None	0	0	None	0	0	0	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	0.6994	likely_pathogenic	0.737	pathogenic	-0.078	Destabilizing	0.916	D	0.522	neutral	None	None	None	None	N
K/C	0.9098	likely_pathogenic	0.9025	pathogenic	-0.413	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	N
K/D	0.841	likely_pathogenic	0.8749	pathogenic	0.115	Stabilizing	0.987	D	0.617	neutral	None	None	None	None	N
K/E	0.529	ambiguous	0.6099	pathogenic	0.146	Stabilizing	0.892	D	0.469	neutral	N	0.501738481	None	None	N
K/F	0.9692	likely_pathogenic	0.9734	pathogenic	-0.231	Destabilizing	0.999	D	0.642	neutral	None	None	None	None	N
K/G	0.7365	likely_pathogenic	0.7577	pathogenic	-0.29	Destabilizing	0.975	D	0.534	neutral	None	None	None	None	N
K/H	0.6039	likely_pathogenic	0.575	pathogenic	-0.467	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	N
K/I	0.8313	likely_pathogenic	0.8665	pathogenic	0.409	Stabilizing	0.983	D	0.655	neutral	N	0.477155683	None	None	N
K/L	0.7692	likely_pathogenic	0.7987	pathogenic	0.409	Stabilizing	0.975	D	0.531	neutral	None	None	None	None	N
K/M	0.6784	likely_pathogenic	0.7221	pathogenic	0.042	Stabilizing	0.999	D	0.651	neutral	None	None	None	None	N
K/N	0.7893	likely_pathogenic	0.8184	pathogenic	-0.002	Destabilizing	0.983	D	0.609	neutral	N	0.495951446	None	None	N
K/P	0.9421	likely_pathogenic	0.961	pathogenic	0.275	Stabilizing	0.033	N	0.325	neutral	None	None	None	None	N
K/Q	0.3442	ambiguous	0.3425	ambiguous	-0.095	Destabilizing	0.983	D	0.609	neutral	N	0.500029114	None	None	N
K/R	0.1027	likely_benign	0.0964	benign	-0.11	Destabilizing	0.944	D	0.527	neutral	N	0.44650406	None	None	N
K/S	0.7399	likely_pathogenic	0.7727	pathogenic	-0.49	Destabilizing	0.916	D	0.539	neutral	None	None	None	None	N
K/T	0.5214	ambiguous	0.5704	pathogenic	-0.299	Destabilizing	0.967	D	0.61	neutral	N	0.497543382	None	None	N
K/V	0.7477	likely_pathogenic	0.7809	pathogenic	0.275	Stabilizing	0.987	D	0.57	neutral	None	None	None	None	N
K/W	0.9655	likely_pathogenic	0.9675	pathogenic	-0.263	Destabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	N
K/Y	0.9157	likely_pathogenic	0.9214	pathogenic	0.088	Stabilizing	0.996	D	0.627	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.