ClinVar Miner

Submissions for variant NM_000312.3(PROC):c.935C>T (p.Ser312Leu) (rs121918160)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000000715 SCV000646390 likely pathogenic Thrombophilia, hereditary, due to protein C deficiency, autosomal dominant 2017-03-09 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 312 of the PROC protein (p.Ser312Leu). The serine residue is moderately conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs121918160, ExAC 0.009%). This variant has been reported in individuals with deep vein thrombosis (DVT), pulmonary embolism (PE), and protein C (PC) deficiency (PMID: 7482420, 22545135). It has also been reported to arise de novo in a proband with DVT, PE, and PC deficiency, whose children inherited this variant and also had low levels of plasma protein C and protein C activity (PMID: 11380450). However, the proband's mother, who did not carry this variant, also had a history of PE. This variant is also known as 8524C>T, p.Ser270Leu in the literature. ClinVar contains an entry for this variant (Variation ID: 680). Experimental studies have shown that this missense change causes defective secretion of protein C (PMID: 11380450). In summary, this variant is a rare missense change that has been observed in affected individuals and shown to disrupt protein function. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000000715 SCV000020865 pathogenic Thrombophilia, hereditary, due to protein C deficiency, autosomal dominant 2001-06-01 no assertion criteria provided literature only

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