TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1883	5872;5873;5874	chr2:178776217;178776216;178776215	chr2:179640944;179640943;179640942
N2AB	1883	5872;5873;5874	chr2:178776217;178776216;178776215	chr2:179640944;179640943;179640942
N2A	1883	5872;5873;5874	chr2:178776217;178776216;178776215	chr2:179640944;179640943;179640942
N2B	1837	5734;5735;5736	chr2:178776217;178776216;178776215	chr2:179640944;179640943;179640942
Novex-1	1837	5734;5735;5736	chr2:178776217;178776216;178776215	chr2:179640944;179640943;179640942
Novex-2	1837	5734;5735;5736	chr2:178776217;178776216;178776215	chr2:179640944;179640943;179640942
Novex-3	1883	5872;5873;5874	chr2:178776217;178776216;178776215	chr2:179640944;179640943;179640942

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-9
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.6686
• 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/T	None	None	1.0	N	0.653	0.53	0.516381326315	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.9252	likely_pathogenic	0.9013	pathogenic	0.024	Stabilizing	0.999	D	0.645	neutral	None	None	None	None	N
K/C	0.9795	likely_pathogenic	0.9801	pathogenic	-0.374	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
K/D	0.9719	likely_pathogenic	0.9623	pathogenic	0.022	Stabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
K/E	0.9192	likely_pathogenic	0.8803	pathogenic	0.024	Stabilizing	0.999	D	0.644	neutral	N	0.470705775	None	None	N
K/F	0.9908	likely_pathogenic	0.9897	pathogenic	-0.234	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
K/G	0.9247	likely_pathogenic	0.9106	pathogenic	-0.148	Destabilizing	1.0	D	0.593	neutral	None	None	None	None	N
K/H	0.8158	likely_pathogenic	0.7861	pathogenic	-0.341	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	N
K/I	0.9614	likely_pathogenic	0.9575	pathogenic	0.395	Stabilizing	1.0	D	0.69	prob.neutral	N	0.514648534	None	None	N
K/L	0.9267	likely_pathogenic	0.9116	pathogenic	0.395	Stabilizing	1.0	D	0.593	neutral	None	None	None	None	N
K/M	0.9112	likely_pathogenic	0.8863	pathogenic	0.106	Stabilizing	1.0	D	0.644	neutral	None	None	None	None	N
K/N	0.9305	likely_pathogenic	0.9074	pathogenic	0.079	Stabilizing	1.0	D	0.687	prob.neutral	N	0.47956244	None	None	N
K/P	0.899	likely_pathogenic	0.8868	pathogenic	0.298	Stabilizing	1.0	D	0.66	neutral	None	None	None	None	N
K/Q	0.6327	likely_pathogenic	0.5538	ambiguous	-0.071	Destabilizing	1.0	D	0.663	neutral	N	0.473016192	None	None	N
K/R	0.1742	likely_benign	0.1696	benign	-0.076	Destabilizing	0.999	D	0.573	neutral	N	0.490022264	None	None	N
K/S	0.9364	likely_pathogenic	0.9178	pathogenic	-0.378	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	N
K/T	0.8562	likely_pathogenic	0.8266	pathogenic	-0.236	Destabilizing	1.0	D	0.653	neutral	N	0.492245011	None	None	N
K/V	0.9374	likely_pathogenic	0.9304	pathogenic	0.298	Stabilizing	1.0	D	0.656	neutral	None	None	None	None	N
K/W	0.9847	likely_pathogenic	0.984	pathogenic	-0.28	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
K/Y	0.9647	likely_pathogenic	0.9621	pathogenic	0.083	Stabilizing	1.0	D	0.648	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.