ClinVar Miner

Submissions for variant NM_019616.4(F7):c.1158T>G (p.His386Gln) (rs121964936)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000012869 SCV001653280 likely pathogenic Factor VII deficiency 2020-06-25 criteria provided, single submitter clinical testing The p.His408Gln variant in F7 has been reported in 3 homozygous and 3 compound heterozygous individuals with factor VII deficiency and segregated with disease in 2 affected individuals from 2 families ( Katsumi 2000 PMID: 10739380, Shen 2001 PMID: 11260055, Jin 2011 PMID: 21287501, Li 2013 PMID: 23358202, Jin 2015 PMID: 25863091, Wang 2018 PMID: 30208845). It has also been identified in 0.033% (6/18114) of East Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In vitro functional studies provide some evidence that this variant impacts protein function (Katsumi 2000 PMID: 10739380); however, these types of assays may not accurately represent biological function. Another variant at the same codon (p.His408Arg) has been identified in individuals with factor VII deficiency, suggesting that change at this position may not be tolerated. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive factor VII deficiency. ACMG/AMP criteria applied: PM3_Strong, PM5, PP1_Moderate, PS3_Supporting.
OMIM RCV000012869 SCV000033110 pathogenic Factor VII deficiency 2002-12-01 no assertion criteria provided literature only

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