ClinVar Miner

Submissions for variant NM_021870.2(FGG):c.1007T>C (p.Met336Thr)

dbSNP: rs121913091
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001797589 SCV002041765 pathogenic Familial dysfibrinogenemia 2021-11-16 criteria provided, single submitter clinical testing Variant summary: FGG c.1007T>C (p.Met336Thr) (legacy name p.Met310Thr) results in a non-conservative amino acid change located in the Fibrinogen, alpha/beta/gamma chain, C-terminal globular domain (IPR002181) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251364 control chromosomes. c.1007T>C has been reported in the literature with different common names such as Fibrinogen Asahi, Fibrinogen Yecheon, Fibrinogen Tokushima II in individuals affected with Congenital Dysfibrinogenemia (example, Yamazumi_1989, Park_2009, Shigekiyo_2012, Miesbach_2010). Some of these reports indicated this variant as a heterozygous de-novo occurrence in the affected proband. It is known to result in subsequent extra N-glycosylation at the gamma Asn 308 (Yamazumi_1989). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
PreventionGenetics, part of Exact Sciences RCV003398534 SCV004121088 pathogenic FGG-related disorder 2022-10-24 criteria provided, single submitter clinical testing The FGG c.1007T>C variant is predicted to result in the amino acid substitution p.Met336Thr. This variant, also known as Met310Thr by legacy nomenclature, has been reported in individuals with Dysfibrinogenemia (Yamazumi et al. 1989. PubMed ID: 2496144; Park et al. 2009. PubMed ID: 19949684; Miesbach et al 2010. PubMed ID: 19923982; Shigekiyo et al. 2012. PubMed ID: 22836217). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as pathogenic.
GeneDx RCV004777563 SCV005390483 likely pathogenic not provided 2024-04-29 criteria provided, single submitter clinical testing Identified in the heterozygous state in patients with dysfibrinogenemia in the published literature, including one apparently de novo occurrence (PMID: 19949684) (PMID: 2496144, 19949684, 19923982, 22836217); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also referred to as fibrinogen Asahi and Yecheon, and by alternate nomenclature p.(M310T); This variant is associated with the following publications: (PMID: 22836217, 19949684, 2496144, 19923982)
OMIM RCV000017786 SCV000038065 other FIBRINOGEN ASAHI 2014-09-26 no assertion criteria provided literature only

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